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Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice.
Nonsteroidal Anti-inflammatory Drug [EPC]
Orphenadrine citrate is a skeletal muscle relaxant used as an adjunct to rest and physical therapy for the relief of discomfort associated with acute, painful musculoskeletal conditions. It acts centrally to reduce muscle spasm and pain through anticholinergic and NMDA antagonist pathways.
Name
Orphenadrine
Raw Name
ORPHENADRINE CITRATE
Category
Nonsteroidal Anti-inflammatory Drug [EPC]
Salt Form
Citrate
Drug Count
5
Variant Count
25
Last Verified
February 17, 2026
RxCUI
994528, 994530, 994521, 994541, 994535, 994539, 994537
UNII
R16CO5Y76E, 3G6A5W338E, X0A40N8I4S
About Orphenadrine
Orphenadrine citrate is a skeletal muscle relaxant used as an adjunct to rest and physical therapy for the relief of discomfort associated with acute, painful musculoskeletal conditions. It acts centrally to reduce muscle spasm and pain through anticholinergic and NMDA antagonist pathways.
Detailed information about Orphenadrine
This page is for informational purposes only and does not replace medical advice. Consult a qualified healthcare professional before using any medication containing Orphenadrine.
Orphenadrine citrate is a centrally acting skeletal muscle relaxant that has been a cornerstone in the management of acute musculoskeletal pain for decades. Chemically related to the antihistamine diphenhydramine, orphenadrine belongs to the ethanolamine antihistamine class but is primarily utilized for its potent anticholinergic and analgesic-potentiating properties rather than its allergy-relief capabilities. According to the FDA-approved labeling, orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.
Historically, orphenadrine was first approved by the U.S. Food and Drug Administration (FDA) in the late 1950s. While it is often grouped with other muscle relaxants like cyclobenzaprine or methocarbamol, its pharmacological profile is distinct. It does not act directly on the skeletal muscles themselves; instead, it exerts its effects within the central nervous system (CNS), specifically targeting the motor centers of the brain and spinal cord to reduce the frequency and intensity of muscle spasms.
In clinical practice, orphenadrine is available as a standalone agent (often under the brand name Norflex) or in combination with other medications. The prompt notes its association with Nonsteroidal Anti-inflammatory Drugs (NSAIDs) and Central Nervous System Stimulants; this is because orphenadrine is frequently co-formulated with aspirin and caffeine (as seen in the brand Norgesic). This combination approach targets pain through multiple pathways: the muscle relaxant addresses the spasm, the NSAID reduces inflammation, and the caffeine acts as an analgesic adjuvant to enhance the pain-relieving effects of the aspirin.
The precise mechanism of action for orphenadrine in humans has not been fully elucidated, but several key pathways have been identified through pharmacological research. Unlike medications like dantrolene, which act directly on the muscle fibers, orphenadrine works primarily at the level of the brainstem and spinal cord.
Understanding how the body processes orphenadrine is essential for safe dosing.
Orphenadrine is indicated for the following:
Orphenadrine is available in several dosage forms to accommodate different clinical needs:
> Important: Only your healthcare provider can determine if Orphenadrine is right for your specific condition. This medication is a prescription-only drug and must be used under strict medical supervision.
The dosage of orphenadrine must be individualized based on the severity of the condition and the patient's response to therapy. According to the standard FDA-approved labeling for Norflex and its generics:
Safety and effectiveness in pediatric patients (under the age of 18) have not been established. Therefore, orphenadrine is generally not recommended for use in children. Healthcare providers will typically explore alternative therapies for musculoskeletal issues in pediatric populations.
Since the metabolites of orphenadrine are primarily excreted by the kidneys, patients with impaired renal function may require lower doses or less frequent administration. There are no specific GFR-based dosing guidelines in the official labeling, but clinical monitoring for increased anticholinergic toxicity is essential.
Orphenadrine is extensively metabolized by the liver. In patients with significant liver disease (e.g., cirrhosis), the clearance of the drug is reduced, leading to higher plasma concentrations and a higher risk of side effects. Healthcare providers may suggest a lower starting dose or longer intervals between doses.
Geriatric patients are particularly sensitive to the anticholinergic and sedative effects of orphenadrine. The American Geriatrics Society (AGS) Beers Criteria lists orphenadrine as a potentially inappropriate medication for the elderly due to the high risk of confusion, falls, and urinary retention. If used, the lowest possible dose should be initiated.
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular dosing schedule. Do not double the dose to catch up, as this significantly increases the risk of side effects and toxicity.
An overdose of orphenadrine is a medical emergency and can be fatal. It is characterized by rapid onset and severe symptoms.
> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, as this may lead to a return of symptoms or unexpected reactions.
Most side effects of orphenadrine are related to its anticholinergic action. These are typically dose-dependent and may diminish as the body adjusts to the medication.
> Warning: Stop taking Orphenadrine and call your doctor immediately or seek emergency care if you experience any of the following:
Orphenadrine is not intended for long-term use. Prolonged use (months or years) can lead to:
There are currently no FDA black box warnings specifically for orphenadrine citrate. However, it carries significant warnings regarding its use in patients with certain pre-existing conditions like glaucoma or myasthenia gravis, which are discussed in the Contraindications section.
Report any unusual symptoms or side effects to your healthcare provider. You may also report side effects to the FDA at 1-800-FDA-1088.
Orphenadrine is a potent medication that affects the central nervous system. It should only be used for the specific condition for which it was prescribed. Because it can cause significant impairment in mental alertness and physical coordination, patients must exercise extreme caution when first starting the drug until they know how it affects them.
No FDA black box warnings for Orphenadrine. While it lacks the highest level of FDA warning, this does not imply that the drug is without risk. It is a high-risk medication for specific populations, particularly the elderly and those with certain ocular or gastrointestinal conditions.
For short-term use (the standard indication), extensive lab monitoring is usually not required. However, for patients on combination products or those with underlying health issues, healthcare providers may monitor:
Orphenadrine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. This effect is magnified when the drug is combined with alcohol or other CNS depressants. Patients should not drive until they are certain the medication does not cause significant drowsiness or dizziness.
Alcohol must be avoided while taking orphenadrine. Alcohol increases the sedative effects of the drug, leading to extreme drowsiness, respiratory depression, and an increased risk of falls or accidents. The combination can also increase the risk of gastrointestinal bleeding if the orphenadrine is part of a combination product containing aspirin.
While orphenadrine is not typically associated with a severe withdrawal syndrome, it should not be stopped abruptly if it has been used at high doses for an extended period. A gradual taper under medical supervision may be recommended to prevent a rebound of muscle spasms or "anticholinergic rebound" symptoms (such as sweating, nausea, and headache).
> Important: Discuss all your medical conditions, especially any history of heart, eye, or bladder problems, with your healthcare provider before starting Orphenadrine.
Certain medications should never be used with orphenadrine due to the risk of severe, life-threatening interactions:
Orphenadrine is not known to significantly interfere with most common laboratory tests. However, if you are taking the combination product containing aspirin, it may affect urine glucose tests (giving false negatives in some methods) or stool occult blood tests.
For each major interaction, the mechanism usually involves either pharmacodynamic synergism (where two drugs do the same thing to the body, doubling the effect) or pharmacokinetic interference (where one drug changes how the other is absorbed or metabolized). Management typically involves avoiding the combination or adjusting the dose while monitoring for toxicity.
> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and allergy meds.
Orphenadrine must NEVER be used in patients with the following conditions, as the risks far outweigh any potential benefits:
In these cases, a healthcare provider will perform a careful risk-benefit analysis:
Patients who are allergic to diphenhydramine (Benadryl) may have a cross-sensitivity to orphenadrine due to their similar chemical structures. If you have had a severe reaction to Benadryl, inform your doctor before starting orphenadrine.
> Important: Your healthcare provider will evaluate your complete medical history, including any "hidden" conditions like undiagnosed eye pressure issues, before prescribing Orphenadrine.
Orphenadrine is classified as FDA Pregnancy Category C. This means that animal reproduction studies have shown an adverse effect on the fetus, or there are no adequate and well-controlled studies in humans. It is unknown whether orphenadrine can cause fetal harm when administered to a pregnant woman.
It is not known whether orphenadrine is excreted in human milk. However, many drugs in this class do pass into breast milk. Because of the potential for serious adverse reactions in nursing infants (such as extreme sleepiness or feeding difficulties), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Orphenadrine is not approved for use in children under 18 years of age. The safety profile has not been established in this group. Pediatric patients may be more susceptible to the CNS side effects, including seizures and paradoxical excitation.
Use in the elderly (65 years and older) requires extreme caution.
In patients with chronic kidney disease, the excretion of orphenadrine metabolites is delayed. While specific dose-adjustment tables are not available, healthcare providers typically start at the lowest possible dose (e.g., 100 mg once daily instead of twice) and monitor for signs of toxicity like blurred vision or urinary retention.
Since the liver is the primary site of metabolism via CYP enzymes, patients with hepatic impairment (Child-Pugh Class B or C) are at high risk for drug accumulation. Frequent monitoring of liver enzymes and clinical status is necessary. If severe liver failure is present, the drug may be contraindicated.
> Important: Special populations require individualized medical assessment. Always disclose your full health status, including pregnancy or plans to become pregnant, to your healthcare team.
Orphenadrine citrate is a centrally acting skeletal muscle relaxant. Its molecular mechanism involves several distinct pathways:
| Parameter | Value |
|---|---|
| Bioavailability | ~90% (Oral) |
| Protein Binding | 95% |
| Half-life | 13–20 hours |
| Tmax | 2 hours (IR), 6-8 hours (ER) |
| Metabolism | Hepatic (CYP2B6, 2D6, 3A4) |
| Excretion | Renal (8% unchanged), Fecal (trace) |
Orphenadrine is classified as a skeletal muscle relaxant and an anticholinergic. Within the therapeutic area of musculoskeletal medicine, it is grouped with other centrally acting agents. Unlike baclofen (a GABA-B agonist) or tizanidine (an alpha-2 agonist), orphenadrine’s primary utility stems from its anticholinergic and NMDA-modulating profile.
Medications containing this ingredient
Common questions about Orphenadrine
Orphenadrine is primarily used to treat muscle pain, spasms, and discomfort caused by strains, sprains, or other muscle injuries. It is considered an adjunctive therapy, meaning it is intended to be used alongside rest and physical therapy rather than as a standalone cure. The medication works within the central nervous system to help relax muscles and improve mobility during the acute phase of an injury. It is not typically used for long-term chronic muscle conditions or spasticity caused by neurological diseases like multiple sclerosis. Your doctor will usually prescribe it for a short duration, often two to three weeks, to help you through the most painful part of recovery.
The most common side effects of orphenadrine are related to its anticholinergic properties, which affect various systems in the body. Many patients experience dry mouth, blurred vision, and a feeling of lightheadedness or dizziness. Drowsiness is also frequent, though it may be less intense than with other muscle relaxants. Some individuals may notice an increased heart rate or a bit of constipation as their digestion slows down. These side effects are usually mild and often go away as your body gets used to the medicine. However, if they become bothersome or severe, you should contact your healthcare provider for guidance.
No, you should strictly avoid drinking alcohol while taking orphenadrine. Both alcohol and orphenadrine act as central nervous system depressants, meaning they slow down brain activity and coordination. When taken together, they can cause extreme drowsiness, severe dizziness, and a significantly increased risk of accidents or falls. Furthermore, the combination can lead to dangerous respiratory depression, where your breathing becomes too shallow or slow. If you are taking a combination product that contains aspirin, alcohol also increases your risk of developing stomach ulcers or gastrointestinal bleeding. Always talk to your doctor about your alcohol consumption before starting this medication.
Orphenadrine is classified as a Pregnancy Category C medication, which means its safety during pregnancy has not been fully established through human clinical trials. Animal studies have suggested there may be risks to the developing fetus, but human data is limited. Generally, healthcare providers only prescribe orphenadrine to pregnant women if the potential benefit clearly outweighs the potential risks. If the medication is a combination product containing aspirin, it is particularly dangerous in the third trimester as it can cause heart problems for the baby and bleeding issues during birth. If you are pregnant or planning to become pregnant, you must discuss alternative pain management options with your obstetrician.
The onset of action for orphenadrine depends on the form in which it is administered. For standard oral tablets, most patients begin to feel some relief within one hour of taking the dose, with peak effects occurring between two and four hours later. If you are taking the extended-release (ER) version, the medication is released slowly to provide steady relief over a 12-hour period. In a hospital setting, an injection of orphenadrine can work much faster, often providing relief within 5 to 15 minutes. It is important to remember that this drug is meant to be part of a broader treatment plan including rest and physical therapy for the best results.
For most patients taking the standard dose for a short period of two weeks or less, stopping orphenadrine suddenly does not usually cause severe withdrawal symptoms. However, if you have been taking high doses or using the medication for an extended period, you should consult your doctor before stopping. Abruptly discontinuing an anticholinergic drug can sometimes lead to a 'rebound' effect, where you experience symptoms like nausea, sweating, headache, and a return of muscle spasms. Your healthcare provider may suggest a gradual reduction in dose over a few days to allow your nervous system to readjust. Always follow the specific instructions provided by your medical professional.
If you miss a dose of orphenadrine, you should take it as soon as you remember. However, if it is already close to the time for your next scheduled dose, you should skip the missed one entirely. Do not take two doses at once to make up for the one you missed, as this can lead to an overdose and increase the risk of serious side effects like hallucinations or a dangerously fast heart rate. Maintaining a consistent schedule helps keep the medication at an effective level in your body. If you find yourself frequently forgetting doses, using a pill organizer or setting a phone alarm can be very helpful strategies.
Weight gain is not a commonly reported side effect of orphenadrine in clinical studies. Unlike some other classes of medications, such as certain antidepressants or antipsychotics, orphenadrine does not typically interfere with metabolism or appetite in a way that leads to significant weight changes. However, because the medication is used to treat painful muscle conditions, patients may become less active while recovering, which could indirectly lead to slight weight changes. If you notice rapid or unusual weight gain while taking this medication, it is more likely related to fluid retention or another underlying issue, and you should discuss it with your healthcare provider.
Orphenadrine can interact with many other medications, so it is vital to provide your doctor with a full list of everything you take. It is particularly dangerous when combined with other drugs that cause sleepiness, such as opioids, sleep aids, or anxiety medications like Xanax. It also interacts with other anticholinergic drugs (like those for overactive bladder or COPD), which can lead to severe dry mouth, confusion, and inability to urinate. If you are taking the combination form of orphenadrine that contains aspirin, you must also be careful with blood thinners like warfarin. Always check with a pharmacist before starting any new over-the-counter supplements or herbal remedies.
Yes, orphenadrine citrate is widely available as a generic medication in both its standalone form and in combination with aspirin and caffeine. The generic versions are bioequivalent to the brand-name versions like Norflex or Norgesic, meaning they have the same active ingredients and work the same way in the body. Generic medications are typically much more affordable and are covered by most insurance plans. When you receive your prescription, the tablets may look different in color or shape depending on the manufacturer, but the clinical effect should remain consistent. Consult your pharmacist if you have questions about the specific generic version you were dispensed.