What You Should Know About Phenytoin XR Side Effects

Phenytoin XR is an effective seizure medication that has been used for decades — but like all medications, it comes with potential side effects. Some are mild and go away on their own. Others are serious and need immediate medical attention.

This guide covers what to expect when taking Phenytoin XR, based on FDA labeling and clinical data, so you can feel informed and prepared.

What Is Phenytoin XR?

Phenytoin XR (extended-release phenytoin sodium) is a hydantoin anticonvulsant used to treat generalized tonic-clonic seizures and complex partial seizures. Brand names include Dilantin Kapseals and Phenytek. It works by blocking sodium channels in the brain, which prevents the spread of abnormal electrical activity that causes seizures.

Phenytoin XR has a narrow therapeutic index, meaning the effective dose and the toxic dose are close together. This is why regular blood level monitoring is essential and why side effects can sometimes be dose-related.

Common Side Effects

These side effects are relatively common, especially when starting Phenytoin XR or after a dose increase. Many improve as your body adjusts:

• Dizziness — One of the most frequently reported side effects. Usually improves over time.
• Drowsiness — You may feel sleepy, especially in the first few weeks.
• Nausea — Taking Phenytoin XR with food can help reduce stomach upset.
• Gingival hyperplasia (gum overgrowth) — Affects up to 50% of long-term users. Good oral hygiene and regular dental care can help manage this.
• Rash — Mild rashes are common. However, any rash should be reported to your doctor because it could be the start of a serious reaction.
• Nystagmus (involuntary eye movements) — Often a sign that your blood level is on the higher end.
• Ataxia (coordination problems) — Difficulty with balance or walking, often dose-related.
• Constipation — Staying hydrated and eating fiber-rich foods can help.
• Hirsutism (excess hair growth) — More commonly reported in women and children.
• Coarsening of facial features — Can occur with long-term use.

Serious Side Effects

These side effects are less common but require immediate medical attention. Contact your doctor or go to the emergency room if you experience any of the following:

• Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) — Severe, life-threatening skin reactions that can start as a rash with blistering. Risk is higher in people with the HLA-B*1502 gene variant, which is more common in people of Southeast Asian descent.
• DRESS syndrome — Drug Reaction with Eosinophilia and Systemic Symptoms. Causes fever, rash, swollen lymph nodes, and organ damage. Usually appears 2–8 weeks after starting Phenytoin XR.
• Hepatotoxicity (liver damage) — Symptoms include yellowing of the skin or eyes (jaundice), dark urine, and severe fatigue.
• Megaloblastic anemia — A blood condition caused by folic acid depletion. Your doctor may recommend folic acid supplements.
• Suicidal thoughts or behavior — The FDA requires a warning on all anticonvulsants about a small increased risk of suicidal thoughts. Tell your doctor immediately if your mood changes significantly.
• Lymphadenopathy — Swollen lymph nodes that can mimic lymphoma. Usually resolves after stopping the drug.
• Decreased bone mineral density — Long-term use of Phenytoin XR can weaken bones, increasing fracture risk. Your doctor may recommend calcium and vitamin D supplements.
• Peripheral neuropathy — Tingling, numbness, or pain in your hands and feet with long-term use.

Specific Populations at Higher Risk

Certain groups need extra monitoring while taking Phenytoin XR:

• Pregnant women — Phenytoin XR is Pregnancy Category D. It can cause fetal hydantoin syndrome, which includes birth defects affecting the face, skull, and limbs. If you're pregnant or planning to become pregnant, talk to your doctor about safer alternatives.
• Elderly patients — Older adults may need lower doses because they metabolize Phenytoin XR more slowly.
• People with low albumin or kidney problems — These conditions can increase the amount of active (free) Phenytoin in your blood, raising the risk of side effects even at "normal" total blood levels.
• People of Southeast Asian descent — Higher risk of SJS/TEN due to the HLA-B*1502 gene variant. Genetic testing is recommended before starting Phenytoin XR.

How to Manage Side Effects

Here are practical tips for dealing with common Phenytoin XR side effects:

• For dizziness and drowsiness — Take your dose at bedtime if your doctor approves. Avoid driving until you know how the medication affects you.
• For nausea — Take Phenytoin XR with food. Avoid taking it on an empty stomach.
• For gum overgrowth — Brush and floss regularly. See your dentist every six months. Tell your dentist you take Phenytoin XR.
• For constipation — Drink plenty of water, eat high-fiber foods, and stay physically active.
• For any rash — Contact your doctor right away. Do not wait to see if it gets worse.

If side effects are significantly affecting your quality of life, talk to your doctor. There may be a dose adjustment or alternative medication that works better for you.

Final Thoughts

Phenytoin XR is a well-established seizure medication, but its narrow therapeutic window means side effects need to be taken seriously. Most common side effects are manageable, but serious reactions — especially skin reactions, liver problems, and mood changes — require prompt medical attention.

Stay in regular contact with your doctor, get your blood levels checked on schedule, and don't hesitate to report anything that doesn't feel right. For help finding Phenytoin XR at a pharmacy near you, visit Medfinder.