Pregabalin

Pregabalin is used to treat nerve pain, fibromyalgia, and seizures — but which conditions it's approved for depends on the specific product.

• Neuropathic pain from diabetic peripheral neuropathy (nerve pain from diabetes): All products — Lyrica capsules, Lyrica oral solution, Lyrica CR, pregabalin capsules, pregabalin oral solution, and pregabalin extended-release tablets
• Postherpetic neuralgia (nerve pain after shingles): All products listed above
• Fibromyalgia: Lyrica capsules, Lyrica oral solution, pregabalin capsules, and pregabalin oral solution only — NOT Lyrica CR or pregabalin extended-release tablets
• Neuropathic pain from spinal cord injury: Lyrica capsules, Lyrica oral solution, pregabalin capsules, and pregabalin oral solution only
• Add-on therapy for partial-onset seizures (patients 1 month and older): Lyrica capsules and Lyrica oral solution only
• Add-on therapy for partial-onset seizures (patients 17 years and older): Pregabalin capsules and pregabalin oral solution only
• Not approved for fibromyalgia or seizures: Lyrica CR and pregabalin extended-release tablets — effectiveness has not been established for these uses

Pregabalin binds tightly to a specific protein on voltage-gated calcium channels in the brain and spinal cord called the alpha-2-delta subunit. By doing this, it appears to reduce the release of pain-signaling chemicals (neurotransmitters) from overactive nerve cells, helping to quiet down the pain signals traveling through the nervous system. It may also work through pain-regulating pathways that run from the brainstem down into the spinal cord. Though it looks chemically similar to GABA — the brain's main calming chemical — pregabalin does not act directly on GABA receptors and works through a different mechanism entirely.

How you take pregabalin depends on which product you're prescribed. Capsules and oral solution are taken two or three times daily and can be taken with or without food. Lyrica CR and pregabalin extended-release tablets are taken once daily after an evening meal and must be swallowed whole — never split, crushed, or chewed. If you miss a dose of an extended-release tablet in the evening, you can take it before bed with a snack; if you miss the bedtime dose, take it after a morning meal.

• Never stop pregabalin suddenly — always taper the dose slowly over at least one week
• Your dose will be adjusted if you have kidney problems, since pregabalin is cleared through the kidneys
• Older adults may need lower doses due to age-related changes in kidney function

The most common side effects of pregabalin tend to be dose-related and usually start shortly after beginning treatment.

• Dizziness — very common; was the most frequent reason people stopped the drug in clinical trials
• Drowsiness (somnolence) — also very common, especially at higher doses
• Dry mouth
• Swelling in the hands, feet, or legs (peripheral edema)
• Weight gain
• Blurred or double vision — usually resolves with continued use
• Trouble concentrating or thinking clearly
• Unsteady walking or poor coordination (ataxia)

Seek medical attention right away for serious reactions: throat or face swelling (angioedema), hives or severe skin reactions, new or worsening depression or suicidal thoughts, or any signs of slow or labored breathing.

• Breathing problems (respiratory depression): Pregabalin can cause serious or even fatal slowing of breathing, especially when combined with opioids or other CNS depressants. This risk also exists — though less commonly — without those combinations.
• Suicidal thoughts and behavior: Like all anti-seizure medicines, pregabalin increases the risk of suicidal thinking. This risk applies to anyone taking it, regardless of the reason. Watch for mood changes, worsening depression, or unusual behavior and report them to your doctor immediately.
• Angioedema and severe allergic reactions: Swelling of the face, mouth, throat, or neck can be life-threatening. Stop the medicine and get emergency help right away if this happens.
• Do not stop suddenly: Abrupt discontinuation can cause withdrawal symptoms (insomnia, nausea, headache, anxiety) and increases seizure risk in people with seizure disorders. Always taper slowly.
• Dizziness and drowsiness: These are common and can impair your ability to drive or use machinery — be cautious until you know how pregabalin affects you.
• Swelling and weight gain: Pregabalin can cause fluid retention and weight gain. This is more pronounced when combined with thiazolidinedione diabetes drugs (such as pioglitazone). Use caution in people with heart failure.

Pregabalin itself is unlikely to affect how other drugs are processed by the liver, but it can add to the effects of drugs that slow the brain or nervous system.

• Opioids (e.g., oxycodone): Increases risk of serious respiratory depression and sedation — both prescribers need to be aware if you take both
• Benzodiazepines and other CNS depressants (e.g., lorazepam): Worsens thinking and motor coordination when combined
• Alcohol: Adds to sedation and impairs cognitive and physical functioning
• Thiazolidinedione diabetes drugs (e.g., pioglitazone, rosiglitazone): Higher rates of swelling and weight gain when combined with pregabalin
• ACE inhibitors: May increase the risk of angioedema (throat/face swelling) in people already on these blood pressure medicines

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Allergy to pregabalin: Do not take pregabalin if you've had a hypersensitivity reaction to it before — this is a contraindication
• Kidney problems: Dose must be reduced in anyone with impaired kidney function, since pregabalin is cleared almost entirely by the kidneys
• Older adults: Kidney function naturally declines with age, so dose adjustment may be needed
• Pregnancy: Observational data suggest a possible small increase in the risk of birth defects; animal studies showed developmental toxicity at high doses. Discuss risks and benefits carefully with your doctor. A pregnancy registry is available (call 1-888-233-2334).
• Breastfeeding: Pregabalin passes into breast milk. Due to a potential risk to the infant, breastfeeding is not recommended while taking pregabalin
• Men trying to father children: Pregabalin may affect sperm characteristics in a small percentage of men; discuss with your doctor
• Heart failure (NYHA Class III or IV): Use with caution; limited safety data exist for this group
• Children: Use in children for seizures is specific to Lyrica (capsules and oral solution) for ages 1 month and older; pregabalin capsules are approved for seizures only in patients 17 and older

Taking too much pregabalin can cause reduced consciousness, confusion, agitation, anxiety, seizures, and heart rhythm problems. Deaths have been reported — both with pregabalin alone and when combined with other CNS depressants. There is no specific antidote; treatment focuses on supportive care and monitoring. Call a Poison Control Center immediately (1-800-222-1222 in the US) or go to the emergency room. Pregabalin can be partially removed by hemodialysis if needed.

Pregabalin reduces the release of pain-signaling chemicals (pro-nociceptive neurotransmitters) from nerve cells in the spinal cord by binding to the alpha-2-delta subunit of calcium channels. This calms the overactive nerve signals that drive chronic nerve pain and may also reduce abnormal electrical activity that contributes to seizures. It does not block sodium channels, is not active at opioid receptors, and does not affect serotonin, dopamine, or noradrenaline reuptake — which distinguishes it from many other pain and mood medications.

Pregabalin is rapidly and reliably absorbed when taken by mouth, with more than 90% of the dose reaching the bloodstream regardless of dose size. When taken without food, it peaks in the blood within about 1.5 hours; food slows absorption but does not reduce the total amount absorbed. The body clears pregabalin almost entirely through the kidneys — about 90% is excreted unchanged in the urine — with a half-life of roughly 6 hours in people with normal kidney function. Because elimination is so closely tied to kidney function, people with kidney disease or older adults with age-related kidney decline will need dose adjustments; hemodialysis also removes about 50% of pregabalin from the body in 4 hours.

Store at 20° to 25° C (68° to 77° F), excursions permitted between 15° to 30° C (59° to 86° F) .