Generality
Phenytoin is an active ingredient used in the treatment of epilepsy and seizures .
It is available in different pharmaceutical formulations, suitable for both oral administration and parenteral administration .
Phenytoin can be included in the composition of medicinal products either individually, as the only active ingredient, or in combination with other active ingredients useful for the treatment of epilepsy (generally, they are barbiturates ). The decision to use one type of medicine rather than another is up to the doctor who will evaluate the needs of each patient.
From the chemical point of view, phenytoin is to be considered as a derivative of hydantoin, another molecule capable of carrying out antiepileptic activities. Not surprisingly, phenytoin is also known as diphenyl hydantoin . The IUPAC name of phenytoin is 5, 5-diphenylimidazolidine-2, 4-dione.
Examples of specialties Medicinal products containing Phenytoin
- Aurantin®
- Dintoina®
- Dintoinale®
- Metinal-Idantoin L
Therapeutic indications
When is the use of Phenytoin indicated?
The indications of phenytoin may be different depending on the concentration of active ingredient present in the medicinal product to be used and depending on the route of administration through which the drug is administered.
Phenytoin parenterally
The use of phenytoin parenterally is indicated in all the following cases:
- Treatment of the tonic-clonic epileptic state (great evil);
- Treatment of convulsions accompanied by loss of consciousness ;
- Prevention and treatment of seizures that can occur during or after a neurosurgical operation, or following traumas to the brain ;
- Treatment of cardiac arrhythmias when conventional therapies have been shown to be ineffective; in particular, when cardiac rhythm disorders are caused by medicines that increase the strength of cardiac contraction (digitalis).
Phenytoin by mouth
The use of phenytoin orally is indicated in the treatment of:
- Primary generalized epileptic seizures (with the exception of the small evil);
- Partial epileptic seizures ;
- Cardiac arrhythmias when first choice drugs have not given satisfactory results;
- Trigeminal neuralgia .
Phenytoin in association with barbiturates
Phenytoin- containing medicines in combination with barbiturates (generally, methylphenobarbital and / or phenobarbital) are indicated in the treatment of:
- Primary generalized epileptic seizures (great evil);
- Partial epileptic seizures ;
- Psychomotor epilepsy .
Please note
The administration of phenytoin and barbiturate medicines in combination only occurs when the individual active ingredients - administered at the appropriate doses - are not able to produce the desired antiepileptic effects.
Warnings
Warnings and precautions for the use of phenytoin
Before starting phenytoin therapy, you must inform your doctor if you are in one or more of the following situations:
- If you suffer from hypotension, heart failure or other cardiovascular diseases ;
- If you suffer from kidney and / or liver disease ;
- You are suffering from diabetes ;
- One is suffering from porphyria ;
- If you are addicted to alcohol .
In any case, as a precautionary measure, before starting the phenytoin-based treatment, it is advisable to inform your doctor of your health conditions and the presence of any type of disorder or pathology.
In addition to what has been said so far, it is important to remember that the doctor must be contacted immediately if - during or immediately after treatment with phenytoin - the following symptoms and symptoms appear:
- Suicidal ideas;
- Cardiac arrhythmias;
- Hypotension;
- Purple glove syndrome (this is a syndrome characterized by edema, skin discoloration and pain);
- Serious skin reactions;
- Thrombocytopenia, leukopenia or pancytopenia;
- Enlarged lymph nodes;
- Disorders of the central nervous system.
Please note
The administration of phenytoin - either alone or in combination with barbiturates - may alter the ability to drive and / or use machines. Therefore, similar activities should be avoided during therapy based on the aforementioned active ingredients.
Pharmacological Interactions
Interactions between Phenytoin and Other Drugs
Before starting phenytoin therapy, due to the possible drug interactions, it is necessary to inform your doctor if you are taking, or have recently been taken, one or more of the following drugs:
- Opioid analgesic drugs;
- Non-steroidal anti-inflammatory drugs (NSAIDs);
- Other anticonvulsant drugs;
- Corticosteroid drugs;
- Benzodiazepines and other psychotropic drugs;
- Antibiotic, antifungal and antiretroviral drugs;
- Anti-cancer chemotherapy;
- Calcium channel blockers and antihypertensive drugs;
- Gastroprotective drugs;
- Statins;
- Immunosuppressive drugs;
- Hypoglycemic drugs;
- Hyperglycemic drugs;
- Oral contraceptives and estrogen-based drugs;
- Anticoagulant drugs;
- Bronchodilators;
- Anesthetic drugs;
- Vitamin D based drugs.
Furthermore, it is necessary to inform the doctor if you are taking products based on hypericum ( Hypericum perforatum, or St. John's wort), a plant with known antidepressant properties, since the active substances contained in it may interfere with the therapeutic action of phenytoin.
Lastly, it should not be forgotten that alcohol intake can decrease phenytoin levels in the blood, consequently reducing its therapeutic activity.
However, it is always a good idea to inform your doctor if you are taking - or have recently taken - any drug or substance of any other type, including prescription free medicines (SOP), OTC drugs, herbal and herbal products and homeopathic products.
Side effects
Side Effects Caused by the Assumption of Phenytoin
Phenytoin may induce several side effects, although not all patients manifest them, or manifest them in the same way. In fact, each individual reacts subjectively to the administration of the drug in question. However, below are some of the main side effects that could occur during phenytoin therapy.
Blood disorders
Phenytoin treatment could cause the appearance of:
- Thrombocytopenia;
- Leukopenia;
- pancytopenia;
- macrocytosis;
- Megaloblastic anemia.
For this reason, regular blood tests are recommended.
Gastrointestinal disorders
Oral phenytoin therapy could give rise to:
- Nausea and vomit;
- Stomach ache;
- Constipation.
However, by taking phenytoin after meals, the onset of the above side effects could be prevented.
Musculoskeletal disorders
The intake of phenytoin - especially if continued for long periods - could favor the appearance of:
- Osteopenia;
- Osteoporosis;
- Increased risk of bone fractures.
Cardiovascular disorders
Administration of intravenous phenytoin may cause:
- Hypotension;
- Atrial and ventricular arrhythmias;
- Cardiovascular collapse;
- Cardiac arrest and, in the most serious cases, death.
Nervous system disorders
Phenytoin therapy - especially if given by intravenous injection - can cause:
- Ataxia;
- Dysarthria;
- nystagmus;
- Reduced coordination;
- Mental confusion.
Other side effects
Other side effects that could occur during treatment with phenytoin consist of:
- Allergic reactions, even serious, in sensitive individuals;
- Stevens-Johnson syndrome and toxic epidermal necrolysis (however, these are very rare reactions);
- In case of parenteral administration, local reactions at the site of administration (irritation, inflammation, pain, soreness, etc.);
- Changes in respiratory function (when phenytoin is administered parenterally);
- Skin rashes (especially in children and young adults);
- Gingival hyperplasia;
- Changes in results from thyroid function tests.
Overdose
In the event of phenytoin overdose, the following symptoms may appear:
- nystagmus;
- He retched;
- Headache;
- Dizziness;
- Drowsiness;
- Speech disorders;
- Mental confusion;
- Loss of muscle coordination;
- Muscle contractions.
Therefore, in case of assumption - ascertained or presumed - of excessive doses of phenytoin, it is necessary to immediately alert the doctor and / or contact the medical help (118).
Action mechanism
How does Phenytoin work?
Phenytoin performs its anticonvulsant action at central level, where it exerts a stabilizing effect on all neuronal membranes, reducing their hyper excitability .
The exact mechanism of action with which phenytoin carries out its activity is not yet fully understood, however, it is likely that it is capable of:
- Reduce sodium conductance, facilitating efflux from neurons;
- Increasing inhibition mediated by GABA (or gamma-aminobutyric acid, it is one of the most important inhibitory neurotransmitters of our nervous system) and reducing excitatory synaptic transmission;
- Reduce the entry of calcium into neurons.
As regards the mechanism of action of phenobarbital and methylphenobarbital which can be administered in association with phenytoin, see the article dedicated to it: Barbiturates.
Method of use and Posology
How to take Phenytoin
Phenytoin is available in medicines suitable for oral use ( tablets ) and suitable for parenteral use ( solution for injection ).
In medicinal products for oral use, phenytoin may be present both as the sole active ingredient and in association with barbiturates such as phenobarbital and / or methylphenobarbital.
Phenytoin solution for injection should be administered by slow intravenous infusion by trained personnel; while the tablets must be swallowed whole with the help of a little water, preferably on a full stomach .
Regarding the dosage of medicine, it must be established by the doctor on a strictly individual basis for each individual patient. In fact, the amount of phenytoin to be administered may vary depending on various factors, such as:
- Age of the patient (phenytoin can also be given to children);
- Body weight of the patient;
- Type of convulsive crisis or other disorder (cardiac arrhythmias or trigeminal neuralgia) that needs to be treated;
- Patient response to the same therapy;
- Ability of the patient to tolerate any side effects.
Patients with liver and / or renal disorders
In patients with liver and / or kidney disease, it may be necessary to reduce the amount of drug administered. For this reason, if you suffer from any of the aforementioned disorders, you must inform your doctor before starting treatment with the drug.
Pregnancy and breastfeeding
Can Phenytoin be taken in pregnancy and during lactation?
Phenytoins can negatively affect the health of the fetus, for this reason, its use is generally contraindicated in pregnant women. In fact, it has been shown that the intake of phenytoin during gestation increases the risk of developing congenital malformations (cleft lip, malformations of the heart and blood vessels, neural tube malformations), tumors and coagulation disorders in the child.
Furthermore, since phenytoin is excreted in breast milk, its use is also contraindicated in breastfeeding women.
Contraindications
When Phenytoin should not be used
Contraindications could be different depending on the route of administration through which phenytoin is taken and depending on the association or otherwise with other drugs (barbiturates).
However, the use of phenytoin as the only active ingredient is generally contraindicated in the following cases:
- In the presence of a known allergy to phenytoin or one or more of the excipients contained within the medicinal product to be used;
- In patients with sinus bradycardia or other cardiac disorders (atrio-ventricular block, sino-atrial block, sinus node syndrome, reduced cardiac output);
- In patients who have had cardiac arrest in the last three months;
- In patients with Adams-Stokes syndrome;
- In patients on therapy with delavirdine (a drug used to treat AIDS);
- In pregnancy and during lactation.
Furthermore, the intake of phenytoin in association with barbiturates is contraindicated even in the following situations:
- In the presence of a known allergy to barbiturates associated with phenytoin;
- In patients with porphyria;
- In the presence of leukopenia;
- In patients with hepatic and / or renal insufficiency;
- In patients suffering from respiratory failure;
- In patients suffering from conduction disorders and cardiac rhythm and / or with injured myocardium;
- In patients poisoned by alcohol, drugs, sleeping drugs (sleeping pills), opioid analgesics and / or psychotropic drugs.
Please note
For detailed information on dosage, side effects and contraindications, we recommend reading the illustrative leaflet of the medicinal product based on phenytoin prescribed by the doctor. Furthermore, if you have any doubts, you should contact this health care professional directly.
