Pregabalin

Pregabalin also called Lyrica is an anti-epileptic drug or an anticonvulsant. Pregabalin is available only with your doctor’s prescription. Pregabalin works by slowing down impulses in the brain that cause seizures or epilepsy. Pregabalin also affects chemicals in the brain that send pain signals across the nervous system or damaged nerves in the body. Pregabalin is used to treat pain caused by fibromyalgia (a long-lasting condition that may cause pain, muscle stiffness and tenderness, tiredness, and difficulty falling asleep or staying asleep) or nerve pain (neuropathic pain from damaged nerves) in people with diabetes called diabetic neuropathy that can occur in your arms, hands, fingers, legs, feet, or toes and herpes zoster post-herpetic neuralgia (the burning, stabbing pain or aches that may last for months or years after an attack of shingles), or spinal cord injury. Pregabalin is also used with other medications (adjunctive therapy) to treat partial-onset seizures in adults and children aged at least 1 month of age and older. Pregabalin will not cure epilepsy and will only work to control seizures for as long as you continue to take it.

Pregabalin is available in capsules in varying concentrations from 25 to 300 mg under the brand name of Lyrica, an oral solution (liquid) and as an extended-release (long-acting) tablet to take by mouth. Pregabalin capsules and oral solution are usually taken with or without food two or three times a day. Pregabalin extended-release tablets are usually taken once daily after an evening meal. Take pregabalin at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.

Swallow the extended-release tablets whole; do not cut, chew, or crush them.

Your doctor will probably start you on a low dose of pregabalin and may gradually increase your dose during the first week of treatment.

Take pregabalin exactly as directed. Pregabalin may be habit forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor.

Pregabalin may help control your symptoms but will not cure your condition. It may take several weeks or longer before you feel the full benefit of pregabalin. Continue to take pregabalin even if you feel well. Do not stop taking pregabalin without talking to your doctor, even if you experience side effects such as unusual changes in behavior or mood. If you suddenly stop taking pregabalin, you may experience withdrawal symptoms, including trouble falling asleep or staying asleep, nausea, diarrhea, headaches, or seizures. Your doctor will probably decrease your dose gradually over at least 1 week.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with pregabalin and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the manufacturer’s website to obtain the Medication Guide.

Most reported adverse effects caused by pregabalin were mild to moderate intensity, dose-dependent, and occurred within the first two weeks of initiating treatment. The most common side effects of pregabalin are dose related and include peripheral swelling (edema), weight gain, dizziness, somnolence, confusion, headache, blurred vision, tremor and ataxia ¹⁾. The most common adverse reactions reported across all patient populations in premarketing controlled trials, which occurred in greater than or equal to 5% of patients taking pregabalin and twice the rate reported by patients receiving placebo, were: somnolence, dizziness, blurred vision, difficulty with concentration/attention, dry mouth, edema, and weight gain ²⁾, ³⁾. Rare but potentially severe adverse events include depression, suicidal ideation and behaviors, angioedema, and hypersensitivity reactions ⁴⁾, ⁵⁾.

Weight gain associated with pregabalin is dose-dependent and occurred in up to 14% of patients receiving 600 mg per day.

Following rapid or abrupt discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache, anxiety, nervousness, irritability, hyperhidrosis, and diarrhea ⁶⁾.

Chronic use of pregabalin can result in physical dependence, and there is a risk of abuse associated with its use, especially in patients on opioid medicines or who have a history of substance abuse ⁷⁾.

Pregabalin special precautions

Pregabalin Warnings

Pregabalin can cause a severe allergic reaction. Stop taking pregabalin and seek emergency medical help if you have hives or blisters on your skin, trouble breathing, or swelling in your face, mouth, or throat.

Some people have thoughts about suicide while taking pregabalin. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

If you have diabetes or heart problems, call your doctor if you have weight gain or swelling in your hands or feet while taking pregabalin.

Do not stop using pregabalin suddenly, even if you feel fine. Stopping suddenly may cause withdrawal symptoms.

Before taking pregabalin:

tell your doctor and pharmacist if you are allergic to pregabalin, any other medications, or any of the ingredients in pregabalin preparations. Ask your pharmacist for a list of the ingredients.
tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: angiotensin converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten, in Capozide), enalapril (Vasotec, in Vaseretic, Lexxel), fosinopril (Monopril), lisinopril (Prinivil, Zestril, in Prinzide, Zestoretic), moexipril (Univasc, in Uniretic), perindopril (Aceon), quinapril (Accupril, in Accuretic, Quinaretic), ramipril (Altace), and trandolapril (Mavik, in Tarka); antidepressants; antihistamines; medications for anxiety including lorazepam (Ativan); medications for mental illness or seizures; certain medications for diabetes such as pioglitazone (Actos, in Duetact) and rosiglitazone (Avandia, in Avandaryl, Avandamet); opioid (narcotic) pain medications including hydrocodone (in Hydrocet, in Vicodin, others), morphine (Avinza, Kadian, MSIR, others), or oxycodone (OxyContin, in Percocet, others); sedatives; sleeping pills; and tranquilizers. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
tell your doctor if you drink or have ever drunk large amounts of alcohol, use or have ever used street drugs, or have overused prescription medications. Also tell your doctor if you have or have ever had swelling of the eyes, face, lips, tongue, or throat; vision problems; heart failure; bleeding problems or a low number of platelets (type of blood cell needed for blood clotting) in your blood, or lung, heart, or kidney disease.
tell your doctor if you are pregnant or if you or your partner plans to become pregnant. Also tell your doctor if you are breastfeeding. If you or your partner becomes pregnant while you are taking pregabalin, call your doctor. Pregabalin has caused decreased fertility in male animals and birth defects in the offspring of male and female animals who were treated with the medication. There is not enough information to tell if pregabalin causes these problems in humans.
if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking pregabalin.
you should know that pregabalin may make you dizzy or drowsy. Do not drive a car operate machinery, or do other dangerous activities until you know how this medication affects you. Ask your doctor when you may do these activities.
do not drink alcohol while taking pregabalin. Alcohol can add to the drowsiness caused by this medication.
you should know that your mental health may change in unexpected ways and you may become suicidal (thinking about harming or killing yourself or planning or trying to do so) while you are taking pregabalin for the treatment of epilepsy, mental illness, or other conditions. A small number of adults and children 5 years of age and older (about 1 in 500 people) who took anticonvulsants such as pregabalin to treat various conditions during clinical studies became suicidal during their treatment. Some of these people developed suicidal thoughts and behavior as early as 1 week after they started taking the medication. There is a risk that you may experience changes in your mental health if you take an anticonvulsant medication such as pregabalin, but there may also be a risk that you will experience changes in your mental health if your condition is not treated. You and your doctor will decide whether the risks of taking an anticonvulsant medication are greater than the risks of not taking the medication. You, your family, or your caregiver should call your doctor right away if you experience any of the following symptoms: panic attacks; agitation or restlessness; new or worsening irritability, anxiety, or depression; acting on dangerous impulses; difficulty falling or staying asleep; aggressive, angry, or violent behavior; mania (frenzied, abnormally excited mood); talking or thinking about wanting to hurt yourself or end your life; withdrawing from friends and family; preoccupation with death and dying; giving away prized possessions; or any other unusual changes in behavior or mood. Be sure that your family or caregiver knows which symptoms may be serious so they can call the doctor if you are unable to seek treatment on your own.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to pregabalin or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Kidney impaired patients

Pregabalin is eliminated primarily by kidney excretion. Adjust the dose in patients with impaired kidney function. According to drug manufacturers the following are recommendations on dose reductions for patients with reduced creatinine clearance (CrCl) and those undergoing hemodialysis.

Creatinine clearance (CrCl) greater than or equal to 60 mL/min- no dose modification recommended
Creatinine clearance (CrCl) 30 – 60 mL/min – 50% dose of recommended daily dose
Creatinine clearance (CrCl) 15- 30 mL/min – 25% dose of recommended daily dose
Creatinine clearance (CrCl) less than or equal to 15 mL/min – 16% to 8% dose of recommended daily dose
Supplementary dosage of approximately an additional 25 mg of recommended daily dose following hemodialysis is recommended

Children

Appropriate studies have not been performed on the relationship of age to the effects of pregabalin in children younger than 1 month of age for partial onset seizures. Safety and efficacy have not been established for other conditions.

Breastfeeding women

Pregabalin has been detected in the milk of lactating women; thus, breastfeeding is not advisable, and an alternative agent is preferred ⁸⁾. There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking Pregabalin while breastfeeding.

Pregnancy

Pregabalin may cause fetal harm. Advise patients there is a potential risk to the fetus ⁹⁾. To monitor pregnancy outcomes in women exposed to pregabalin during pregnancy and provide information on the effects of in utero exposure to pregabalin, clinicians should help enroll pregnant patients in the North American Antiepileptic Drug Pregnancy Registry (https://www.aedpregnancyregistry.org).

Liver Impairment

Although not explicitly studied, because pregabalin is not protein-bound, it is unlikely that patients with hepatic impairment require dosing modifications.

Elderly patients

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of pregabalin in the elderly. However, elderly patients are more likely to have unwanted effects (eg, dizziness, blurred vision, confusion, or clumsiness) and age-related kidney problems, which may require an adjustment in the dose for patients receiving pregabalin.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking pregabalin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using pregabalin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Acepromazine
Alfentanil
Alprazolam
Amobarbital
Anileridine
Aripiprazole
Asenapine
Baclofen
Benperidol
Benzhydrocodone
Bromazepam
Buprenorphine
Buspirone
Butabarbital
Butorphanol
Calcifediol
Calcium Oxybate
Cannabidiol
Carbinoxamine
Carisoprodol
Carphenazine
Chloral Hydrate
Chlordiazepoxide
Chlorpromazine
Chlorzoxazone
Clobazam
Clonazepam
Clorazepate
Clozapine
Codeine
Cyclobenzaprine
Dexmedetomidine
Diacetylmorphine
Diazepam
Dichloralphenazone
Difenoxin
Dihydrocodeine
Diphenhydramine
Diphenoxylate
Doxylamine
Droperidol
Enflurane
Esketamine
Estazolam
Eszopiclone
Ethchlorvynol
Ethopropazine
Ethylmorphine
Fentanyl
Flibanserin
Fluphenazine
Flurazepam
Fluspirilene
Fospropofol
Gabapentin
Gabapentin Enacarbil
Halazepam
Haloperidol
Halothane
Hexobarbital
Hydrocodone
Hydromorphone
Hydroxyzine
Isoflurane
Ketamine
Ketazolam
Ketobemidone
Levorphanol
Lorazepam
Loxapine
Magnesium Oxybate
Meclizine
Melperone
Meperidine
Mephobarbital
Meprobamate
Meptazinol
Mesoridazine
Metaxalone
Methadone
Methdilazine
Methocarbamol
Methohexital
Methotrimeprazine
Methylene Blue
Midazolam
Molindone
Moricizine
Morphine
Morphine Sulfate Liposome
Nalbuphine
Nicomorphine
Nitrazepam
Nitrous Oxide
Olanzapine
Opium
Opium Alkaloids
Orlistat
Orphenadrine
Oxazepam
Oxycodone
Oxymorphone
Papaveretum
Paregoric
Pentazocine
Pentobarbital
Perampanel
Perazine
Periciazine
Perphenazine
Phenobarbital
Pimozide
Piperacetazine
Pipotiazine
Piritramide
Potassium Oxybate
Prazepam
Primidone
Prochlorperazine
Promazine
Promethazine
Propofol
Quazepam
Quetiapine
Ramelteon
Remifentanil
Remimazolam
Remoxipride
Secobarbital
Sertindole
Sodium Oxybate
Sufentanil
Sulpiride
Suvorexant
Tapentadol
Temazepam
Thiethylperazine
Thiopental
Thiopropazate
Thioridazine
Tilidine
Tizanidine
Tolonium Chloride
Topiramate
Tramadol
Triazolam
Trifluoperazine
Trifluperidol
Triflupromazine
Trimeprazine
Zaleplon
Zolpidem
Zopiclone
Zotepine

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

How does pregabalin work?

Pregabalin is an alkylated analogue of gamma-aminobutyric acid (GABA) and is structurally related to gabapentin. However, pregabalin does not directly bind to GABA-A or GABA-B receptors ¹⁰⁾. Additionally, Pregabalin is not metabolized to a GABA receptor agonist. In animal models, pregabalin binds to presynaptic voltage-gated calcium channels at the alpha-2-delta subunit in central nervous system tissues. The binding of the alpha-2-delta subunit decreases the depolarization-induced influx of calcium into neurons and reduces the release of excitatory neurotransmitters by hyperexcited neurons ¹¹⁾, ¹²⁾, ¹³⁾. This action may account for the anticonvulsant and analgesic effects of pregabalin. Pregabalin has no known activity at sodium channels, dopamine receptors, serotonin receptors, opiate receptors and does not modify cyclooxygenase activity ¹⁴⁾.

Pregabalin has antiepileptic, analgesic, and anxiolytic effects. Pregabalin has been shown to be effective in reducing neuropathic pain from diabetic and postherpetic neuropathy and is an effective anticonvulsant ¹⁵⁾.

Pregabalin works in different ways:

In epilepsy Pregabalin stops seizures by reducing the abnormal electrical activity in your brain
With nerve pain Pregabalin blocks pain by affecting the pain messages traveling through your brain and down your spinal cord
In anxiety Pregabalin stops your brain from releasing the chemicals that make you feel anxious.

Pregabalin uses

Pregabalin was approved for use in the United States in 2004 to treat epilepsy and anxiety. Pregabalin is an anticonvulsant and neuropathic pain agent. Pregabalin works in the central nervous system (CNS) to control seizures and pain. Pregabalin is used with other medicines to help control partial-onset seizures (convulsions) in the treatment of epilepsy in patients 1 month of age and older. Pregabalin will not cure epilepsy and will only work to control seizures for as long as you continue to take it.

Pregabalin United States Food and Drug Administration (FDA)-approved indications ¹⁶⁾, ¹⁷⁾, ¹⁸⁾, ¹⁹⁾:

Treatment of nerve pain or neuropathic pain associated with diabetic peripheral neuropathy (diabetic neuropathy or pain caused by nerve damage from diabetes)
Treatment of nerve pain or neuropathic pain associated with spinal cord injury
Neuropathic pain originating from postherpetic neuralgia (nerve pain that occurs after shingles)
Treatment of fibromyalgia (muscle pain and stiffness).
Adjunctive therapy for partial-onset seizures in adults with epilepsy

Pregabalin Off-label Uses ²⁰⁾, ²¹⁾, ²²⁾:

Generalized anxiety disorder
Social anxiety disorder
Bipolar disorder
Insomnia
Chronic pain conditions
Chronic Pruritus (chronic itch)
Chronic cough
Migraine
Restless leg syndrome

There is significant disagreement regarding the effectiveness of pregabalin for the psychiatric disorders listed above. Therefore, prescribers should be careful and monitor patients for therapeutic success when treating patients with pregabalin ²³⁾.

Pregabalin dosage

Pregabalin is only available on prescription. It comes as capsules, tablets (extended release) or a liquid that you swallow. Take Ppregabalin exactly as prescribed by your doctor and read all medication guides or instruction sheets about pregabalin. Your doctor may occasionally change your dose. Pregabalin recommended initial dose for neuropathic pain is 50 to 75 mg two to three times daily, the maximum dose being 300 mg daily. Higher doses are used in treating seizures. The dose should be increased and tapered gradually.

Take pregabalin exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

Pregabalin capsule or oral liquid may be taken with or without food.

Take the extended-release tablet after an evening meal. Swallow it whole. Do not crush, break, or chew it.

Measure the oral liquid using a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Call your doctor if your symptoms do not improve, or if they get worse.

Do not stop using pregabalin suddenly, even if you feel fine. Stopping suddenly may cause increased seizures or unpleasant withdrawal symptoms. Follow your doctor’s instructions about tapering your dose for at least 1 week before stopping completely.

In case of emergency, wear or carry medical identification to let others know you take seizure medication.

Store at room temperature away from moisture, heat, and light.

The dose of pregabalin will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of pregabalin. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.