Orphenadrine XR Side Effects: What to Expect and When to Call Your Doctor

Orphenadrine XR (orphenadrine citrate extended-release 100 mg) is generally well-tolerated when taken as prescribed, but like all medications it carries a risk of side effects. Most side effects are related to its anticholinergic properties — meaning they result from the drug blocking certain nerve signals that control involuntary body functions. This guide helps you know what to expect, how to manage common side effects, and when a side effect is serious enough to warrant a call to your doctor.

Common Side Effects of Orphenadrine XR

These side effects are common and often improve as your body adjusts to the medication. They are mainly due to orphenadrine's mild anticholinergic action and are usually associated with higher doses:

Dry mouth: Often the first side effect to appear. Sip water frequently, chew sugar-free gum, or use artificial saliva products to manage this.

Drowsiness: Avoid driving or operating heavy machinery until you know how Orphenadrine XR affects your alertness, especially when first starting the medication. Alcohol significantly worsens this effect.

Dizziness or lightheadedness: Rise slowly from sitting or lying positions to reduce dizziness. Some patients experience brief episodes of faintness (syncope), especially early in treatment.

Constipation: Stay well-hydrated, eat high-fiber foods, and walk regularly. If severe, ask your doctor about a gentle stool softener.

Blurred vision: Usually temporary. Do not drive or read fine print if your vision is significantly impaired.

Headache: Often mild; over-the-counter pain relief (acetaminophen) can help if not contraindicated.

Nausea or upset stomach: Taking Orphenadrine XR with food can reduce stomach irritation.

Urinary hesitancy or difficulty urinating: More common in men with prostate enlargement. If you have difficulty urinating, notify your prescriber — this is a contraindication to continued orphenadrine use.

Fast heartbeat (tachycardia) or palpitations: May occur especially at higher doses. Tell your doctor if your heart is racing or you feel palpitations.

Dilated pupils and increased eye pressure: Due to anticholinergic effects on the eye. This is why Orphenadrine XR is contraindicated in patients with glaucoma.

Serious Side Effects: Call Your Doctor or Seek Emergency Care

The following side effects are rare but serious. Contact your doctor immediately or call 911 if you experience:

Signs of an allergic reaction: Hives, difficulty breathing, swelling of the face, lips, tongue, or throat. This can be anaphylaxis — a life-threatening emergency.

Hallucinations or confusion: These are signs of CNS toxicity or anticholinergic excess. Stop the medication and call your doctor.

Severe agitation or tremors. This can occur especially if combined with other CNS medications.

Complete inability to urinate (urinary retention): This is a medical emergency that may require catheterization. Go to an ER immediately.

Signs of aplastic anemia (very rare): Unusual bruising or bleeding, extreme fatigue, frequent infections. Very rare cases have been reported — no causal relationship has been established.

Overdose Warning

Orphenadrine is toxic in overdose. The minimum lethal dose in adults has been reported to be 2–3 grams, though toxicity is variable. An overdose typically causes a severe anticholinergic toxidrome: rapid heartbeat, fever, dry flushed skin, dilated pupils, urinary retention, confusion, and seizures. If you or someone else has taken too much, call Poison Control at 1-800-222-1222 immediately or go to the emergency room.

Side Effects in Older Adults

Patients over 65 are at increased risk for all anticholinergic side effects. Orphenadrine appears on the AGS Beers Criteria list of medications generally avoided in older adults. Confusion, falls, urinary retention, and constipation are all heightened risks in this population. Discuss safer alternatives with your prescriber if you are elderly.

Managing Side Effects: Practical Tips

Take the evening dose at bedtime to allow drowsiness to occur while you sleep.

Stay well hydrated to manage dry mouth and constipation.

Avoid alcohol and other CNS depressants — these worsen drowsiness and sedation significantly.

If side effects are intolerable at 100 mg BID, ask your doctor about dose reduction or switching to a different muscle relaxant.

Also be sure to check our guide on Orphenadrine XR drug interactions — many side effects are worsened by combining this medication with other drugs.