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PENTRAN is a brand name for Phenytoin. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Control of tonic-clonic seizures (grand mal epilepsy), partial seizures (focal including temporal lobe) or a combination of these, and the prevention and treatment of seizures occurring during or following neurosurgery and/or severe head injury. Phenytoin has also been employed in the treatment of trigeminal neuralgia…
Verbatim from this product's MHRA label. Tap a section to expand.
Posology The dosage should be adjusted to the individual patient's needs and should be determined by the clinical response and serum phenytoin levels. Phenytoin should be introduced in small dosages with gradual increments until control is achieved or until toxic effects appear.
In some cases serum level determinations may be necessary for optimal dosage adjustments. Therapeutic plasma levels usually range from 10 to 20 μg/ml (40 to 80 μmol/l), although some cases of tonic-clonic seizures may be controlled with lower serum levels of phenytoin.
With recommended dosages a period of seven to ten days may be required to achieve steady state serum levels with phenytoin and changes in dosage should not be carried out at intervals shorter than seven to ten days. Maintenance of treatment should be the lowest dose of anticonvulsant consistent with control of seizures.
Although 100 mg of phenytoin sodium is equivalent to 92 mg of phenytoin on a molecular weight basis, these molecular equivalents are not necessarily biologically equivalent. Physicians should therefore exercise care in those situations where it is necessary to change the dosage form and serum level monitoring is advised.
Adults Initially 3 to 4 mg/kg/day with subsequent dosage adjustment if necessary. An initial dose of 100 mg 2 to 4 times daily is suggested. This can be increased at intervals of 7 to 10 days to a maximum of 600 mg daily. The usual maintenance dose is 200 to 500 mg daily in divided doses.
Exceptionally, a daily dose outside this range may be indicated. Dosage should normally be adjusted according to serum levels where assay facilities exist. Special populations Paediatric population Infants and children Initially, 5mg/kg/day in two divided doses, with subsequent dosage individualised to a maximum of 300mg daily.
A recommended daily maintenance dosage is usually 4- 8mg/kg. Neonates The absorption of phenytoin following oral administration in neonates is unpredictable. Furthermore, the metabolism of phenytoin may be depressed. It is therefore especially important to monitor serum levels in the neonate.
Elderly As with adults the dosage of phenytoin should be titrated to the patient's individual requirements using the same guidelines unless serum albumin is low or hepatic or renal dysfunction is present. Polypharmacy is common in the elderly therefore the possibility of drug interactions should be borne in mind.
List of adverse reactions The following side effects due to phenytoin have been reported. It is essential that the phenytoin induced aetiology of some of these side effects is carefully differentiated from their other aetiologies. The frequency of adverse events according to the following: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Immune System reactions Not known: polyarteritis nodosa Anaphylactoid reaction and anaphylaxis. Hypersensitivity syndrome has been reported and may in rare cases be fatal (the syndrome may include, but is not limited to, symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy or rash), systemic lupus erythematosus, polyarteritis nodosa, and immunoglobulin abnormalities may occur.
Several individual case reports have suggested that there may be an increased, although still rare, incidence of hypersensitivity reactions, including skin rash and hepatotoxicity, in black patients.
Nervous system disorders:
The most common manifestations encountered with phenytoin therapy are referable to this system and are usually dose-related. These include nystagmus, ataxia, slurred speech, decreased co-ordination, mental confusion, paraesthesia, somnolence, drowsiness, and vertigo.
Dizziness, insomnia, transient nervousness, motor twitchings, taste perversion and headaches have also been observed. There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs.
There are occasional reports of irreversible cerebellar dysfunction associated with severe phenytoin overdosage. A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy. Aggression, cerebellar degeneration, cognitive impairment, depression, encephalopathy, fatigue, numbness, paradoxical seizures.
Suicidal ideation and behaviour have been reported in patients treated with anti- epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour.
The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for phenytoin. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.
Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge Withdrawal: Phenytoin should be withdrawn slowly as sudden withdrawal may precipitate status epilepticus.
When, in the judgement of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative anti-epileptic medication arises, this should be done gradually. However, in the event of an allergic or hypersensitivity reaction, rapid substitution of alternative therapy may be necessary.
In this case, alternative therapy should be an anti-epileptic drug not belonging to the hydantoin chemical class. Phenytoin is highly protein bound and extensively metabolised by the liver. Reduced dosage to prevent accumulation and toxicity may therefore be required in patients with impaired liver function.
Where protein binding is reduced, as in uraemia, total serum phenytoin levels will be reduced accordingly. However, the pharmacologically active free drug concentration is unlikely to be altered. Therefore, under these circumstances therapeutic control may be achieved with total phenytoin levels below the normal range of 10-20μg/ml (40-80 μmol/l).
Patients with impaired liver function, elderly patients or those who are gravely ill may show early signs of toxicity.
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Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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If it is necessary to transfer a patient from phenytoin to other anticonvulsant therapy, this is best effected over a period of one week with gradual withdrawal of phenytoin. 6 Pregnancy), measurement of phenytoin levels are valuable as its altered absorption and/or metabolism may require dose adjustments.
Dosage in hepatic and renal impairment Phenytoin is highly protein bound and extensively metabolised by the liver. Reduced dosage to prevent accumulation and toxicity may therefore be required in patients with impaired liver function.
Reduced doses may also be necessary in patients with renal impairment. 5). Method of administration For oral administration.
4) Not known: Hirsutism, hypertrichosis, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash is the most common; dermatitis is seen more rarely.
Other more serious and rare forms have included Stevens-Johnson syndrome and bullous, exfoliative, purpuric dermatitis, lupus erythematosus or toxic epidermal necrolysis. 4). Blood and lymphatic system disorders Haemopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin.
These have included liver damage, megaloblastic, thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression, and aplastic anaemia. Not known: pure red cell aplasia While macrocytosis and megaloblastic anaemia have occurred, these conditions usually respond to folic acid therapy There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local and generalised) including benign lymph node hyperplasia, pseudolymphoma, reduced serum IgA levels, polyarteritis nodosa, lymphoma, and Hodgkin’s Disease.
Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. g. fever, rash and liver involvement.
In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs. Frequent blood counts should be carried out during treatment with phenytoin.
Eye disorders Not known:
Diplopia Respiratory, thoracic and mediastinal disorders Not known: Pneumonitis Gastrointestinal disorders Not known: Nausea, vomiting and constipation, gingival hyperplasia Hepatobiliary disorders Not known: Liver damage, hepatitis toxic Renal and urinary disorders Not known: Nephritis interstitial General disorders and administration site conditions Not known: Fatigue Musculoskeletal and connective tissue disorders: Not known: Systemic lupus erythematosus, polyarthropathy, rickets and osteomalacia, coarsening of the facial features, enlargement of the lips, and Dupuytren's contracture.
There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with phenytoin. The mechanism by which phenytoin affects bone metabolism has not been identified. Vitamin D supplements should be given to patients on long term phenytoin therapy.
Reproductive system and breast disorders Not known:
Peyronie's disease Paediatric population The adverse event profile of phenytoin is generally similar between children and adults. Gingival hyperplasia occurs more frequently in paediatric patients and in patients with poor oral hygiene.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcardor search for MHRA Yellow Card in the Google Play or Apple App Store.
Ineffective in petit mal:
Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence seizures are present together, combined drug therapy is needed. Phenytoin may precipitate or aggravate absence seizures and myoclonic seizures.
Glucose metabolism:
Phenytoin may affect glucose metabolism and inhibit insulin release. Hyperglycaemia has been reported in association with toxic levels. Phenytoin is not indicated for seizures due to hypoglycaemia or other metabolic causes.
CNS toxicity:
Serum levels of phenytoin sustained above the optimal range may produce confusional states referred to as “delirium”, “psychosis”, or “encephalopathy”, or rarely irreversible cerebellar dysfunction. Accordingly, at the first sign of acute toxicity, serum drug level determinations are recommended.
Dose reduction of phenytoin therapy is indicated if serum levels are excessive; if symptoms persist, termination of therapy with phenytoin is recommended. Early signs of toxicity may be observed in patients with impaired liver function, elderly patients or those who are gravely ill.
5). Anticonvulsant Hypersensitivity Syndrome (AHS) is a rare drug induced, multiorgan syndrome which is potentially fatal and occurs in some patients taking anticonvulsant medication. It is characterized by fever, rash, lymphadenopathy, and other multiorgan pathologies, often hepatic.
The mechanism is unknown. The interval between first drug exposure and symptoms is usually 2-4 weeks but has been reported in individuals receiving anticonvulsants for 3 or more months. Patients at higher risk for developing AHS include black patients, patients who have a family history of or who have experienced this syndrome in the past, and immuno-suppressed patients.
The syndrome is more severe in previously sensitized individuals. If a patient is diagnosed with AHS, discontinue the phenytoin and provide appropriate supportive measures. Serious skin reactions - Life-threatening cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with the use of Phenytoin Sodium.
- Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment. g. progressive skin rash often with blisters or mucosal lesions) are present, Phenytoin Sodium treatment should be discontinued.
- The best results in managing SJS and TEN come from early diagnosis and immediate discontinuation of any suspect drug. Early withdrawal is associated with a better prognosis. - If the patient has developed SJS or TEN with the use of Phenytoin Sodium, Phenytoin Sodium must not be re-started in this patient at any time.
Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should seek medical advice from their physician immediately when observing any indicative signs or symptoms.
Phenytoin should be discontinued if a rash appears, and should not be resumed if the rash is exfoliative, purpuric or bullous, or if lupus erythematosus or Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected. If the rash is of a milder type (measles like or scarlatiniform), therapy may be resumed after the rash has completely disappeared.
If the rash recurs upon reinstitution of therapy, further phenytoin medication is contraindicated. Published literature has suggested that there may be an increased, although still rare, risk of hypersensitivity reactions, including skin rash, SJS, TEN, and hepatotoxicity in black patients.
Studies in patients of Chinese ancestry have found a strong association […]