Individual generic drug information

phenytoin

Reference monograph

Part of registered formulation

PHENYTOIN

Reference record: Phenytoin
Source: BNF 80 (2020–2021)
Printed source pages: 361, 362, 363
Age groups indexed: 2

Individual active ingredientSource records are displayed separately

Some source sections could not be separated reliably in the extraction. Review the printed source pages when a field is missing or incomplete.

Overview

Extracted information for Phenytoin only.

Indications And Dose

Tonic-clonic seizures | Focal seizures ▶BY MOUTH ▶Child 1 month–11 years: Initially 1.5–2.5 mg/kg twice daily, then adjusted according to response to 2.5–5 mg/kg twice daily (max. per dose 7.5 mg/kg twice daily), dose also adjusted according to plasma- phenytoin concentration; maximum 300 mg per day ▶Child 12–17 years: Initially 75–150 mg twice daily, then adjusted according to response to 150–200 mg twice daily (max. per dose 300 mg twice daily), dose also adjusted according to plasma-phenytoin concentration Tonic-clonic seizures | Focal seizures | Prevention and treatment of seizures during or following neurosurgery or severe head injury ▶BY MOUTH ▶Adult: Initially 3–4 mg/kg daily, alternatively 150–300 mg once daily, alternatively 150–300 mg daily in 2 divided doses; usual maintenance 200–500 mg daily, to be taken preferably with or after food, dose to be increased gradually as necessary (with plasma- phenytoin concentration monitoring), exceptionally, higher doses may be used Prevention and treatment of seizures during or following neurosurgery or severe head injury ▶BY MOUTH ▶Child: Initially 2.5 mg/kg twice daily, then adjusted according to response to 4–8 mg/kg daily, dose also Nervous system adjusted according to plasma-phenytoin concentration; maximum 300 mg per day Status epilepticus | Acute symptomatic seizures associated with head trauma or neurosurgery ▶INITIALLY BY SLOW INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION ▶Child 1 month–11 years: Loading dose 20 mg/kg, then (by slow intravenous injection or by intravenous infusion) 2.5–5 mg/kg twice daily ▶Child 12–17 years: Loading dose 20 mg/kg, then (by intravenous infusion or by slow intravenous injection) up to 100 mg 3–4 times a day ▶Adult: Loading dose 20 mg/kg (max. per dose 2 g), then (by intravenous infusion or by slow intravenous injection or by mouth) maintenance 100 mg every 6–8 hours adjusted according to plasma-concentration monitoring DOSE EQUIVALENCE AND CONVERSION ▶Preparations containing phenytoin sodium are not bioequivalent to those containing phenytoin base (such as Epanutin Infatabs ® and Epanutin ® suspension); 100 mg of phenytoin sodium is approximately equivalent in therapeutic effect to 92 mg phenytoin base. The dose is the same for all phenytoin products when initiating therapy. However, if switching between these products the difference in phenytoin content may be clinically signiﬁcant. Care is needed when making changes between formulations and plasma-phenytoin concentration monitoring is recommended. l UNLICENSED USE ▶With oral use in children Licensed for use in children (age range not speciﬁed by manufacturer). ▶With intravenous use Phenytoin doses in BNF publications may differ from those in product literature.

Source page 361

Contra Indications

GENERAL CONTRA-INDICATIONS Acute porphyrias p. 1120 SPECIFIC CONTRA-INDICATIONS ▶With intravenous use Second- and third-degree heart block. sino-atrial block. sinus bradycardia. Stokes-Adams syndrome

Source page 361

Cautions

GENERAL CAUTIONS Enteral feeding (interrupt feeding for 2 hours before and after dose; more frequent monitoring may be necessary) SPECIFIC CAUTIONS ▶With intravenous use Heart failure. hypotension. injection solutions alkaline (irritant to tissues). respiratory depression. resuscitation facilities must be available CAUTIONS, FURTHER INFORMATION Consider vitamin D supplementation in patients who are immobilised for long periods or who have inadequate sun exposure or dietary intake of calcium. Intramuscular phenytoin should not be used (absorption is slow and erratic).

Source pages 361, 362

Allergy And Cross Sensitivity

Cross-sensitivity reported with carbamazepine. Antiepileptic hypersensitivity syndrome associated with phenytoin. See under Epilepsy p. 321 for more information.

Source page 362

Pre Treatment Screening

HLAB* 1502 allele in individuals of Han Chinese or Thai origin—avoid unless essential (increased risk of Stevens- Johnson syndrome).

Source page 362

Prescribing And Dispensing Information

Switching between formulations Different formulations of oral preparations may vary in bioavailability. Patients being treated for epilepsy should be maintained on a speciﬁc manufacturer’s product.

Source page 362

Safety

Extracted information for Phenytoin only.

Important Safety Information

NHS IMPROVEMENT PATIENT SAFETY ALERT: RISK OF DEATH AND SEVERE HARM FROM ERROR WITH INJECTABLE PHENYTOIN (NOVEMBER 2016) Use of injectable phenytoin is error-prone throughout the prescribing, preparation, administration and monitoring processes; all relevant staff should be made aware of appropriate guidance on the safe use of injectable phenytoin to reduce the risk of error.

Source page 361

Interactions

→Appendix 1: antiepileptics

Source page 362

Side Effects

Nervous system GENERAL SIDE-EFFECTS Agranulocytosis. bone disorders. bone fracture. bone marrow disorders. cerebrovascular insufﬁciency. coarsening of the facial features. confusion. constipation. dizziness. drowsiness. Dupuytren’s contracture. dysarthria. eosinophilia. fever. gingival hyperplasia (maintain good oral hygiene). granulocytopenia. hair changes. headache. hepatic disorders. hypersensitivity. insomnia. joint disorders. leucopenia. lip swelling. lymphatic abnormalities. macrocytosis. megaloblastic anaemia. movement disorders. muscle twitching. nausea . neoplasms. nephritis tubulointerstitial. nervousness. nystagmus. paraesthesia. Peyronie’s disease. polyarteritis nodosa. pseudolymphoma. sensory peripheral polyneuropathy. severe cutaneous adverse reactions (SCARs). skin reactions. systemic lupus erythematosus (SLE). taste altered. thrombocytopenia. tremor. vertigo. vomiting SPECIFIC SIDE-EFFECTS ▶With oral use Electrolyte imbalance. pneumonitis. vitamin D deﬁciency ▶With parenteral use Arrhythmias. atrial conduction depression (more common if injection too rapid). cardiac arrest. extravasation necrosis. hypotension. injection site necrosis. purple glove syndrome. respiratory arrest (more common if injection too rapid). respiratory disorders. tonic seizure (more common if injection too rapid). ventricular conduction depression (more common if injection too rapid). ventricular ﬁbrillation (more common if injection too rapid) SIDE-EFFECTS, FURTHER INFORMATION Rash Discontinue; if mild re-introduce cautiously but discontinue immediately if recurrence. Bradycardia and hypotension With intravenous use; reduce rate of administration if bradycardia or hypotension occurs. Overdose Symptoms of phenytoin toxicity include nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia.

Source page 362

Pregnancy

See also Pregnancy in Epilepsy p. 321. Monitoring Changes in plasma-protein binding make interpretation of plasma-phenytoin concentrations difﬁcult—monitor unbound fraction. Doses should be adjusted on the basis of plasma-drug concentration monitoring.

Source page 362

Breast Feeding

Small amounts present in milk, but not known to be harmful.

Source page 362

Hepatic Impairment

Manufacturer advises caution (increased risk of accumulation and toxicity due to decreased protein binding in hepatic impairment, hypoalbuminaemia, or hyperbilirubinaemia). Dose adjustments ▶With oral use Manufacturer advises consider dose reduction. ▶With intravenous use Manufacturer advises consider maintenance dose reduction.

Source page 362

Monitoring Requirements

▶Blood counts Manufacturer recommends blood counts (but evidence of practical value uncertain). ▶In adults The usual total plasma-phenytoin concentration for optimum response is 10–20 mg/litre (or 40–80 micromol/litre). In pregnancy, the elderly, and certain disease states where protein binding may be reduced, careful interpretation of total plasma-phenytoin concentration is necessary; it may be more appropriate to measure free plasma-phenytoin concentration. ▶In children Therapeutic plasma-phenytoin concentrations reduced in ﬁrst 3 months of life because of reduced protein binding. Trough plasma concentration for optimum response: neonate–3 months, 6–15 mg/litre (25–60 micromol/litre); child 3 months–18 years, 10–20 mg/litre (40–80 micromol/litre). ▶With intravenous use Monitor ECG and blood pressure.

Source page 362

Dose and formulations

Extracted information for Phenytoin only.

Directions For Administration

Manufacturer advises each injection or infusion should be preceded and followed by an injection of Sodium Chloride 0.9% through the same needle or catheter to avoid local venous irritation. ▶With intravenous use in children g For intravenous injection, give into a large vein at a rate not exceeding 1 mg/kg/minute (max. 50 mg/minute). k Manufacturer advises for intravenous infusion, dilute to a concentration not exceeding 10 mg/mL with Sodium Chloride 0.9% and give into a large vein through an in-line ﬁlter (0.22–0.50 micron). g Give at a rate not exceeding 1 mg/kg/minute (max. 50 mg/minute). k Complete administration within 1 hour of preparation. ▶With intravenous use in adults Manufacturer advises for intravenous injection, give into a large vein at a rate not exceeding 50 mg/minute; rate of 25 mg/minute or lower may be more appropriate in some patients (including the elderly and those with heart disease). Manufacturer advises for intravenous infusion, dilute in 50–100 mL Sodium Chloride 0.9% (ﬁnal concentration not to exceed 10 mg/mL) and give into a large vein through an in-line ﬁlter (0.22–0.50 micron) at a rate not exceeding 50 mg/minute; rate of 25 mg/minute or lower may be more appropriate in some patients (including the elderly and those with heart disease). Complete administration within 1 hour of preparation.

Source page 362

Medicinal Forms

There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: chewable tablet, oral suspension, oral solution Tablet CAUTIONARY AND ADVISORY LABELS 8 ▶Phenytoin (Non-proprietary) Phenytoin sodium 100 mg Phenytoin sodium 100mg tablets | 28 tablet P £30.00 DT = £10.07 Solution for injection EXCIPIENTS: May contain Alcohol, propylene glycol ELECTROLYTES: May contain Sodium ▶Phenytoin (Non-proprietary) Phenytoin sodium 50 mg per 1 ml Phenytoin sodium 250mg/5ml solution for injection ampoules | 5 ampoule P £24.40 (Hospital only) ▶Epanutin (Upjohn UK Ltd) Phenytoin sodium 50 mg per 1 ml Epanutin Ready-Mixed Parenteral 250mg/5ml solution for injection ampoules | 10 ampoule P £48.79 (Hospital only) Oral suspension CAUTIONARY AND ADVISORY LABELS 8 ▶Epanutin (Upjohn UK Ltd) Phenytoin 6 mg per 1 ml Epanutin 30mg/5ml oral suspension | 500 ml P £4.27 DT = £4.27 Chewable tablet CAUTIONARY AND ADVISORY LABELS 8, 24 ▶Epanutin (Upjohn UK Ltd) Phenytoin 50 mg Epanutin Infatabs 50mg chewable tablets | 200 tablet P £13.18 DT = £13.18 Capsule CAUTIONARY AND ADVISORY LABELS 8 ▶Phenytoin (Non-proprietary) Phenytoin sodium 25 mg Phenytoin sodium 25mg capsules | 28 capsule P £7.24 DT = £7.24 Phenytoin sodium 50 mg Phenytoin sodium 50mg capsules | 28 capsule P £7.07 DT = £7.07 Phenytoin sodium 100 mg Phenytoin sodium 100mg capsules | 84 capsule P £67.50 DT = £11.32 Phenytoin sodium 300 mg Phenytoin sodium 300mg capsules | 28 capsule P £9.11 DT = £9.11

Source pages 362, 363

Clinical care

Extracted information for Phenytoin only.

Patient And Carer Advice

Blood or skin disorders Patients or their carers should be told how to recognise signs of blood or skin disorders, and advised to seek immediate medical attention if symptoms such as fever, rash, mouth ulcers, bruising, or bleeding develop. Leucopenia that is severe, progressive, or associated with clinical symptoms requires withdrawal (if necessary under cover of a suitable alternative). Medicines for Children leaflet: Phenytoin for preventing seizures www.medicinesforchildren.org.uk/phenytoin-preventing- seizures

Source page 362

Dose text by age group

Filter the extracted dose blocks for this individual drug.

Children

First line only; read the complete Indications and dose section above.

Initially 1.5–2.5 mg/kg twice

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Initially 75–150 mg twice daily, then

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Adults

First line only; read the complete Indications and dose section above.

Initially 3–4 mg/kg daily, alternatively

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Initially 2.5 mg/kg twice daily, then adjusted

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Loading dose 20 mg/kg, then (by

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Loading dose 20 mg/kg, then (by

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Adults

First line only; read the complete Indications and dose section above.

Loading dose 20 mg/kg (max. per dose 2 g), then

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Age labels are extracted from the printed dose headings and require clinical review. Confirm current local guidance, dose, route, formulation, contraindications and interactions before prescribing.

Individual generic drug information

phenytoin

Reference monograph

Part of registered formulation

PHENYTOIN

Reference record: Phenytoin
Source: BNF 80 (2020–2021)
Printed source pages: 361, 362, 363
Age groups indexed: 2

Individual active ingredientSource records are displayed separately

Some source sections could not be separated reliably in the extraction. Review the printed source pages when a field is missing or incomplete.

Overview

Extracted information for Phenytoin only.

Indications And Dose

Source page 361

Contra Indications

Source page 361

Cautions

Source pages 361, 362

Allergy And Cross Sensitivity

Cross-sensitivity reported with carbamazepine. Antiepileptic hypersensitivity syndrome associated with phenytoin. See under Epilepsy p. 321 for more information.

Source page 362

Pre Treatment Screening

HLAB* 1502 allele in individuals of Han Chinese or Thai origin—avoid unless essential (increased risk of Stevens- Johnson syndrome).

Source page 362

Prescribing And Dispensing Information

Source page 362

Safety

Extracted information for Phenytoin only.

Important Safety Information

Source page 361

Interactions

→Appendix 1: antiepileptics

Source page 362

Side Effects

Source page 362

Pregnancy

Source page 362

Breast Feeding

Small amounts present in milk, but not known to be harmful.

Source page 362

Hepatic Impairment

Source page 362

Monitoring Requirements

Source page 362

Dose and formulations

Extracted information for Phenytoin only.

Directions For Administration

Source page 362

Medicinal Forms

Source pages 362, 363

Clinical care

Extracted information for Phenytoin only.

Patient And Carer Advice

Source page 362

Dose text by age group

Filter the extracted dose blocks for this individual drug.

Children

First line only; read the complete Indications and dose section above.

Initially 1.5–2.5 mg/kg twice

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Initially 75–150 mg twice daily, then

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Adults

First line only; read the complete Indications and dose section above.

Initially 3–4 mg/kg daily, alternatively

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Initially 2.5 mg/kg twice daily, then adjusted

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Loading dose 20 mg/kg, then (by

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Children

First line only; read the complete Indications and dose section above.

Loading dose 20 mg/kg, then (by

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Adults

First line only; read the complete Indications and dose section above.

Loading dose 20 mg/kg (max. per dose 2 g), then

This is a first-line fragment. Read the full Indications and Dose section above.

Candidate age grouping · source page 361

Age labels are extracted from the printed dose headings and require clinical review. Confirm current local guidance, dose, route, formulation, contraindications and interactions before prescribing.