To determine the level of the drug phenytoin in your blood in order to maintain a therapeutic level and to detect potential for toxicity
At regular intervals to monitor; as needed to detect low or toxic concentrations
A blood sample drawn from a vein
None; however, be sure your healthcare practitioner knows about all medications (prescribed and over-the-counter), herbs, and supplements you are taking.
This test measures the amount of phenytoin in the blood.
Phenytoin is a drug prescribed to treat or prevent the recurrence of certain types of seizures (see Epilepsy), including complex partial seizures (impaired consciousness that is preceded, accompanied, or followed by psychological symptoms) or generalized tonic-clonic seizures (involve abrupt loss of consciousness, respiratory arrest, muscle rigidity). It has been widely used in the United States since its development in 1938. It is still being prescribed but is beginning to be replaced by newer drugs. Phenytoin may be used alone or with phenobarbital or other anticonvulsants.
Phenytoin blood testing is ordered because phenytoin blood levels must be maintained within a narrow therapeutic range. If levels are too low, the affected person may experience seizures; if they are too high, the person may experience symptoms associated with phenytoin toxicity. These may include loss of balance and falling, involuntary eye movement from side to side (nystagmus), confusion, slurred speech, tremors, and low blood pressure.
Maintaining a therapeutic level of phenytoin in the blood can be a challenge due to several reasons:
Phenytoin's total effect can be unpredictable. Dosages must be adjusted slowly until a steady concentration in the blood is reached. The time to attain a steady-state level of phenytoin may vary from several days to several weeks because of substantial variations among patients in the amount of time it takes to metabolize phenytoin. Healthcare practitioners must also watch for side effects and adverse reactions during initial dosage adjustment and over time. In some cases, the severity of side effects may make it necessary to consider treating a patient with an alternative anti-seizure medication.
The phenytoin test is used to optimize drug therapy, monitor the amount of phenytoin in the blood, determine whether drug concentrations are in the therapeutic range, and to monitor patient adherence.
It may be ordered every few days when a person first begins taking phenytoin to help adjust the dose to the desired blood level. The test is then ordered at regular intervals and as needed to monitor blood concentrations. One or more phenytoin tests may be ordered if a person starts or stops taking additional medications (to judge their effect, if any, on phenytoin levels) and may be ordered if the person has a seizure or if a healthcare practitioner suspects toxicity.
Under normal conditions, a total phenytoin test is appropriate for monitoring therapeutic levels because the balance between bound and unbound phenytoin in the blood is relatively stable.
In certain conditions and disease states (e.g., renal disease, low blood levels of albumin), a free phenytoin test may be considered. These conditions and disease states can lead to an increase of "free" phenytoin and thus patients may experience symptoms of toxicity even though their total phenytoin results fall within the therapeutic range.
Phenytoin is ordered frequently when a person begins phenytoin treatment and when/if a person's medications change (other drugs are started, stopped, or changed) or if there is a change in the status of the person's health. Once stable blood concentrations in the therapeutic range have been achieved, phenytoin is monitored at regular intervals to ensure that it remains in this range.
The test may be ordered when a person's condition does not appear to be responding to phenytoin (e.g., the person continues to have seizures) to determine whether the concentration is too low, the medication is ineffective, and/or to determine if the person is complying with therapy (taking the phenytoin regularly).
The test may also be ordered when a person experiences side effects or exhibits symptoms that the healthcare practitioner suspects may be due to toxicity. Toxic symptoms can affect the mouth, cardiovascular and nervous systems, and the eyes and include:
A free phenytoin level may be ordered when a person has a condition in which the percentage of free or active phenytoin may be increased. Some examples of these conditions include:
Test results may vary depending on the person's age, gender, health history, the method used for the testing and co-administrated medications.
The therapeutic ranges for most adults have been established at 10.0-20.0 mcg/mL for total phenytoin (bound plus unbound) and 1.0-2.0 mcg/mL for free phenytoin (unbound only). This reference range for unbound phenytoin (free) was established based on an assumed 10% unbound drug fraction. However, the free fraction of phenytoin can vary from 3% to 37% among patients.
In general, when phenytoin results are in the therapeutic range, most patients will respond to the drug without symptoms of toxicity. Response and side effects will be individual, however. Some people will experience seizures at the low end of the therapeutic range and some people will experience excessive side effects at the upper end. People should work closely with their healthcare practitioner to find the dosage and concentration that works the best for them. Dosage determinations and adjustments must be evaluated on a case-by-case basis.
People who take phenytoin long-term may develop vitamin D deficiency, numbness in their extremities due to nerve damage (peripheral neuropathy), acne, excessive hair on their face or body, a thickening of facial features, or weakness of their bones. Rarely, a person may develop a severe rash and skin condition that requires hospitalization.
Women who use phenytoin during pregnancy are at an increased risk of having babies born with several types of birth defects, such as growth problems, heart defects, and cleft palate. Women who want to become pregnant should talk to their healthcare practitioner.
Phenytoin is sometimes prescribed for other conditions such as trigeminal neuralgia, which causes episodes of sharp pain along the jaw, and other causes of nerve pain. This use must also be monitored.
Phenytoin is not effective for patients with absence seizures (impaired consciousness, often abrupt onset and brief).
A large variety of prescribed drugs, over-the-counter medications, and supplements can increase, decrease, or interfere with the concentration of phenytoin in the blood and its effects.
Many more drugs interact with phenytoin, so tell your healthcare practitioner about any prescription or over-the-counter drugs, supplements, or herbal products you take. Patients should not increase, decrease, or stop taking their medication without consulting with their healthcare provider as it can increase their risk of having a seizure and may affect other medications that they are taking.
Phenytoin or another anti-seizure medication is usually taken every day (sometimes several times a day) for a person's lifetime. An exception to this may be people whose seizures are caused by a temporary condition; they may only need the medication for a short period of time.
It may be taken as a pill or a liquid. When a person has status epilepticus (an acute, continuing seizure), then phenytoin is given intravenously for rapid action.
No, it requires specialized equipment. Blood samples are collected from a vein in the arm and tested in the laboratory.
Sources Used in Current Review
2018 review completed by Fang Wu, PhD, DABCC, Clinical Biochemist, Saskatchewan Health Authority.
Olson KR, Anderson IB, Benowitz NL, Blanc PD, Clark RF, Kearney TE, Kim-Katz SY, Wu AB. Olson K.R., Anderson I.B., Benowitz N.L., Blanc P.D., Clark R.F., Kearney T.E., Kim-Katz S.Y., Wu A.B. Eds. Kent R. Olson, et al. eds. Poisoning & Drug Overdose, 7e New York, NY: McGraw-Hill.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns DE, eds. St. Louis: Elsevier Saunders.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
(2003 April 1, Revised). Phenytoin Oral. MedlinePlus Drug Information [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682022.html.
Whetstone, W. (2005 May 10, Revised). Phenytoin Overdose. MedlinePlus Drug Information [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682022.html.
Wilner, A. (2004 October 11). The Epilepsy Continuum: From Age to Age. Medscape [On-line CME]. Available online at http://www.medscape.com/viewarticle/489615.
Pack, A. (2006 April 28). Therapy Insight: Clinical Management of Pregnant Women With Epilepsy. Medscape from Nat Clin Pract Neurol. 2006;2(4):190-200 [On-line information]. Available online at http://www.medscape.com/viewarticle/530483.
Holloway, R. and Jozefowicz, R. (2006 March). Update in Neurology. Ann Intern Med 2006:144:421-426 [On-line journal]. PDF available for download at http://www.annals.org/cgi/reprint/144/6/421.pdf.
(© 2006). Phenytoin, Free & Total. ARUP's Laboratory Test Directory [On-line information]. Available online at http://www.aruplab.com/guides/ug/tests/0090141.jsp.
Morantz, C. and Torrey, B. (2005 January 15). Guidelines for Prescribing Antiepileptic Drugs. American Family Physician: v71(2) [On-line information]. Available online at http://www.aafp.org/afp/20050115/practice.html.
(© 2006). Phenytoin. Epilepsy.com [On-line information]. Available online at http://www.epilepsy.com/medications/a_phenytoin_intro.html.
(2003 February 1, revised). Seizure Disorders. Merck Manual Home Edition [On-line information]. Available online at http://www.merck.com/mmhe/print/sec06/ch085/ch085a.html.
McMillin GA; Juenke J; Dasgupta A ( Oct. 2005). Effect of ultrafiltrate volume on determination of free phenytoin concentration. Medscape from Ther Drug Monit. 2005; 27(5):630-3 (ISSN: 0163-4356). Available online at http://www.medscape.com/medline/abstract/16175137.
Dasgupta A (Oct. 2002). Clinical utility of free drug monitoring. Medscape from Clin Chem Lab Med. 2002; 40(10):986-93 (ISSN: 1434-6621). Available online at http://www.medscape.com/medline/abstract/12476936.
(Dec 30, 2008). von Winckelmann S, Spriet I, Willems L. Therapeutic Drug Monitoring of Phenytoin in Critically Ill Patients. MedScape. Available online at http://www.medscape.com/viewarticle/583862. Accessed Sept 2010.
(Updated July 15, 2009). Miller C. Toxicity, Phenytoin. Medscape eMedicine. Available online at http://emedicine.medscape.com/article/816447-overview. Accessed September 2010.
(Updated May 1, 2009). Phenytoin. MedlinePlus Drug Information [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682022.html. Accessed September 2010.
(Updated February 3, 2009). Duldner J, Phenytoin Overdose. Medline Plus Drug Information. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/002533.htm. Accessed September 2010.
Malaty W, Stiglemen S. Antiepileptic Drug Monitoring. Am Fam Physician. 2008 Aug 1;78(3):385-386. Available online at http://www.aafp.org/afp/2008/0801/p385.html. Accessed September 2010.
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns DE, eds. St. Louis: Elsevier Saunders; 2006 Pp 1252, 2313.
Carl GF, Smith ML. Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin. Epilepsia 1992; 33(2):372-5. Available online at http://www.medscape.com.
Beckmann, Charles R, et al. Obstetrics and Gynecology. 4th Ed. Baltimore: Lippincott Williams & Wilkins, 2002.
Phenytoin. Medline Plus. Available online at http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682022.html. Last Revised 05/01/2009. Accessed February 13, 2014.
Dilantin. RxList.com. Available online at http://www.rxlist.com/dilantin-drug.htm. Last updated February 7, 2014. Accessed February 13, 2014.
Charlene Miller et al. Phenytoin Toxicity Clinical Presentation. Medscape. Available online at http://emedicine.medscape.com/article/816447-clinical#a0217. Last updated November 9, 2012. Accessed February 13, 2014.
Phenytoin (Phenytek, Dilantin). NYU Langone Medical Center. Available online at http://epilepsy.med.nyu.edu/treatment/medications/phenytoin#sthash.5jYjrrwC.dpbs. Accessed February 13, 2014.