Horizant vs. Gralise: How Do They Compare for Nerve Pain?
Key takeaways:
Horizant and Gralise are gabapentin medications that last longer in the body than immediate-release gabapentin.
These products are effective for nerve pain from shingles (Horizant and Gralise) and restless leg syndrome (Horizant only). But they haven’t been proven effective for other types of pain.
There are ways to save on Horizant and Gralise. For instance, GoodRx can help you access Horizant at an exclusive cash price of about $170. Manufacturer savings cards are also available.
Table of contents
Gabapentin is a medication that treats many medical conditions. It comes as an immediate-release (IR) form (Neurontin) and two extended-release (ER) forms called Horizant and Gralise.
Horizant and Gralise were FDA-approved in 2011. These medications are longer-acting than IR gabapentin and don’t have to be taken as often throughout the day. They may also be less likely to cause side effects.
Here, we’ll compare Horizant and Gralise effectiveness, side effects, and more.
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What is Horizant?
Horizant is a brand-name-only tablet that contains gabapentin enacarbil, a prodrug of gabapentin. Prodrugs like gabapentin enacarbil turn into the active form of the medication once they enter the body.
Horizant is FDA-approved to treat nerve pain from shingles (postherpetic neuralgia) and restless leg syndrome (RLS) in adults.
What is Gralise?
Gralise is another gabapentin product. Like Horizant, it’s a brand-name-only, ER tablet that lasts longer in the body than IR gabapentin. It’s approved to treat postherpetic neuralgia in adults. It contains the same active ingredient as IR gabapentin (it’s not a prodrug like Horizant).
How do gabapentin products work for nerve pain?
We don’t know exactly how gabapentin works to relieve nerve pain.
The structure of gabapentin is similar to a brain chemical called gamma-aminobutyric acid (GABA). GABA slows down nerve activity and relaxes the body. This may be how gabapentin relieves nerve pain.
What are the dosages for Horizant and Gralise?
Horizant and Gralise are dosed differently, and it’s important to know that Horizant, Gralise, and IR gabapentin aren’t interchangeable. For example, taking 600 mg of Horizant is not the same as taking 600 mg of Gralise or 600 mg of IR gabapentin.
Keep in mind: You may experience withdrawal side effects like headache, nausea, and diarrhea if you stop one of these medications abruptly. Stopping them too quickly can also lead to seizures. Your healthcare provider will instruct you on how to slowly lower your dose of these medications if necessary.
Horizant
When Horizant is taken for postherpetic neuralgia, the typical starting dose is 600 mg every morning with food for 3 days. Then, the dose is usually increased to 600 mg twice daily with food.
If Horizant is prescribed for RLS, the usual dose is 600 mg once daily at around 5PM with food.
Gralise
For postherpetic neuralgia, your healthcare provider will likely start you on a low dose of Gralise (300 mg) and slowly raise the dose over the course of 2 weeks or more (up to 1,800 mg). Gralise comes as a “starter pack” that contains a dose titration guide to help you with the initial dosage schedule.
Regardless of your dose, Gralise is taken once a day with the evening meal.
How effective are Horizant and Gralise at treating nerve pain?
Clinical studies have shown that Horizant and Gralise effectively treat nerve pain. We’ll take a look at how well they work for their FDA-approved uses below.
Postherpetic neuralgia
Clinical trials compared various doses of Horizant with placebo (a pill with nothing in it). After 12 weeks of treatment, over 300 people rated their pain. All Horizant doses were more effective at improving pain than placebo. And a 1,200 mg dose of Horizant was just as effective as higher doses.
Another clinical trial looked at over 450 people taking Gralise 1,800 mg daily or a placebo pill for 8 weeks. People taking Gralise had more improvement in pain than the people taking a placebo.
We don’t have much research that compares Horizant and Gralise for postherpetic neuralgia. But it’s been found that Horizant leads to more steady gabapentin levels in the body over the course of a day. And Horizant generally requires a lower daily dose (600 mg to 1,200 mg of Horizant versus 1,800 mg of Gralise). This could potentially minimize side effects.
RLS
Horizant was studied for RLS treatment in two 12-week clinical trials. Both Horizant 600 mg and 1,200 mg were studied. Both doses were better than placebo at relieving symptoms of RLS.
Other types of pain
There’s not much research on Horizant and Gralise for other types of pain. While some small studies of Gralise have found that it may be effective for other types of pain, they were small studies and they didn’t have the best study design.
However, another study looking at Gralise for nerve pain from diabetes found that it did reduce pain. This was a slightly larger study of close to 150 people. And it was a randomized controlled trial (the best type of study to look for cause and effect).
Keep in mind: IR gabapentin is recommended as a first-choice treatment for some types of nerve pain, such as diabetic nerve pain. But how well it works for other types of pain is unclear. It also hasn’t been shown to be the best option for types of chronic pain, including back pain.
Are gabapentin products approved for chronic pain?
No gabapentin products are FDA-approved for chronic pain. Chronic pain is defined as consistent pain, or pain that comes and goes for at least 3 months.
While gabapentin might be prescribed off-label to treat different types of pain, there’s not much evidence that gabapentin is effective at treating chronic pain. This is especially true for pain that isn’t nerve-related.
Common side effects of Horizant and Gralise
The most common side effects of Horizant and Gralise are listed in the table below. These percentages are based on clinical studies in which people received 600 mg or 1,200 mg per day of Horizant, and up to 1,800 mg per day of Gralise.
Side effect | ||
Tiredness | 20%-27% | 5% |
Dizziness | 13%-22% | 11% |
Headache | 15% (with 1,200 mg dose) | Similar to placebo |
Irritability | 4% | Not reported |
Fluid buildup | 3% (with 1,200 mg dose) | 4% |
Weight gain | Similar to placebo | 2% |
Dry mouth | 4% (with 1,200 mg dose) | 3% |
Urinary tract infection | Not reported | 2% |
Decreased sexual desire | 2% (with 1,200 mg dose) | Not reported |
Serious side effects of Horizant and Gralise
Some side effects of Horizant and Gralise can be more serious and require medical attention. Luckily, these aren’t as common as the side effects discussed above.
Suicidal thoughts and behavior
These medications may cause an increase in suicidal thoughts and behavior. This can happen as early as 1 week after starting Horizant or Gralise. Talk to your healthcare provider if you experience new or worsening depression or any mood changes.
If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.
Breathing problems
Horizant and Gralise can cause life-threatening breathing problems when taken with other medications or substances that slow down the brain or your breathing. This includes alcohol, opioids, and benzodiazepines. It’s best to avoid this combination of medications if possible.
Difficulty with activities that require focus
Because Horizant and Gralise commonly cause dizziness and drowsiness, this can affect your ability to perform certain activities, including driving. When starting these medications or increasing your dose, avoid driving and other activities that require alertness until you see how the medications affect you.
What interactions do Horizant and Gralise have?
Horizant and Gralise may interact with certain medications. Most notably, gabapentin can be dangerous when combined with other sedating medications and substances. As discussed above, this includes opioids, benzodiazepines, and alcohol. In fact, some opioids can increase the levels of Gralise in the body, and alcohol can increase levels of Horizant.
It’s also best to avoid sleep medications like zolpidem (Ambien) and even over-the-counter medications that cause drowsiness like diphenhydramine (Benadryl) while taking Horizant or Gralise.
Ways to save on Horizant and Gralise
There are ways to save on Horizant and Gralise. GoodRx can help you navigate between GoodRx coupons and copay savings cards to save money on your prescription.
Save with GoodRx: Anyone with a valid prescription can use GoodRx to purchase a 30-day supply of Horizant at an exclusive cash price of about $170.
Save with a copay savings card: If you have commercial insurance, you may be eligible to pay as little as $0 for Horizant or $20 for Gralise using a savings card from the manufacturer.
The bottom line
Gralise and Horizant are extended-release forms of gabapentin. These products are approved to treat postherpetic neuralgia. Horizant is also approved to treat restless leg syndrome. Horizant is taken one to two times a day, and Gralise is usually taken once a day.
Both are effective at treating postherpetic neuralgia, and Horizant is effective at treating restless leg syndrome. But it’s unclear how effective gabapentin products are for other types of pain.
The most common side effects of Horizant and Gralise are dizziness and tiredness. They can also cause more serious side effects like suicidal thoughts and behavior, trouble breathing, and severe allergic reactions.
Why trust our experts?
References
American Diabetes Association Professional Practice Committee. (2021). Retinopathy, neuropathy, and foot care: Standards of Medical Care in Diabetes - 2022. Diabetes Care.
Assertio Therapeutics, Inc. (2020). Gralise [package insert].
Azurity Pharmaceuticals, Inc. (2020). Horizant [package insert].
Jewett, B. E., et al. (2022). Physiology, GABA. StatPearls.
Kaye, A. D., et al. (2014). The effects of gastroretentive gabapentin (Gralise®) on spinal stenosis patients with radicular pain. Pain Physician.
Knezevic, N. N., et al. (2019). The effect of once-daily gabapentin extended release formulation in patients with postamputation pain. Frontiers in Pharmacology.
North, J. M., et al. (2015). The effect of a novel form of extended-release gabapentin on pain and sleep in fibromyalgia subjects: An open-label pilot study. Pain Practice.
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