Pregabalin

Pregabalin is described chemically as (S)-3-(aminomethyl)-5-methylhexanoic acid. The molecular formula is C8H17NO2 and the molecular weight is 159.23. The chemical structure of pregabalin is:

Pregabalin is a white to off-white, crystalline solid with a pKa1 of 4.2 and a pKa2 of 10.6. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05M phosphate buffer) at pH 7.4 is - 1.35.

LYRICA (pregabalin) Capsules are administered orally and are supplied as imprinted hard-shell capsules containing 25, 50, 75, 100, 150, 200, 225, and 300 mg of pregabalin, along with lactose monohydrate, cornstarch, and talc as inactive ingredients. The capsule shells contain gelatin and titanium dioxide. In addition, the orange capsule shells contain red iron oxide and the white capsule shells contain sodium lauryl sulfate and colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells. The imprinting ink contains shellac, black iron oxide, propylene glycol, and potassium hydroxide.

LYRICA (pregabalin) oral solution, 20 mg/mL, is administered orally and is supplied as a clear, colorless solution contained in a 16 fluid ounce white HDPE bottle with a polyethylene-lined closure. The oral solution contains 20 mg/mL of pregabalin, along with methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water as inactive ingredients.

LYRICA
(LEER-i-kah)
(pregabalin) Capsules

LYRICA
(LEER-i-kah)
(pregabalin) Oral Solution

Read this Medication Guide before you start taking LYRICA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about LYRICA, ask your healthcare provider or pharmacist.

What is the most important information I should know about LYRICA?

LYRICA may cause serious side effects including:

• Serious, even life-threatening, allergic reactions
• Swelling of your hands, legs and feet
• Suicidal thoughts or actions
• Dizziness and sleepiness

These serious side effects are described below:

• Serious, even life-threatening, allergic reactions.
  Stop taking LYRICA and call your healthcare provider right away if you have any of these signs of a serious allergic reaction:
  • swelling of your face, mouth, lips, gums, tongue, throat or neck
  • trouble breathing
  • rash, hives (raised bumps) or blisters
• Like other antiepileptic drugs, LYRICA may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:
  • thoughts about suicide or dying
  • attempts to commit suicide
  • new or worse depression
  • new or worse anxiety
  • feeling agitated or restless
  • panic attacks
  • trouble sleeping (insomnia)
  • new or worse irritability
  • acting aggressive, being angry, or violent
  • acting on dangerous impulses
  • an extreme increase in activity and talking (mania)
  • other unusual changes in behavior or mood

If you have suicidal thoughts or actions, do not stop LYRICA without first talking to a healthcare provider.

• Stopping LYRICA suddenly can cause serious problems.
• Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

How can I watch for early symptoms of suicidal thoughts and actions?

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.
• Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
• Swelling of your hands, legs and feet. This swelling can be a serious problem for people with heart problems.
• Dizziness and sleepiness. Do not drive a car, work with machines, or do other dangerous activities until you know how lyrica affects you. Ask your healthcare provider about when it will be okay to do these activities.

What is LYRICA?

LYRICA is a prescription medicine used in adults, 18 years and older, to treat:

• pain from damaged nerves (neuropathic pain) that happens with diabetes
• pain from damaged nerves (neuropathic pain) that follows healing of shingles
• partial seizures when taken together with other seizure medicines
• fibromyalgia (pain all over your body)
• pain from damaged nerves (neuropathic pain) that follows spinal cord injury

It is not known if LYRICA is safe and effective in children.

Who should not take LYRICA?

Do not take LYRICA if you are allergic to pregabalin or any of the ingredients in LYRICA.

See “What is the most important information I should know about LYRICA?” for the signs of an allergic reaction.

See the end of this leaflet for a complete list of ingredients in LYRICA.

What should I tell my healthcare provider before taking LYRICA?

Before taking LYRICA, tell your healthcare provider about all your medical conditions, including if you:

• have or have had depression, mood problems or suicidal thoughts or behavior
• have kidney problems or get kidney dialysis
• have heart problems including heart failure
• have a bleeding problem or a low blood platelet count
• have abused prescription medicines, street drugs, or alcohol in the past
• have ever had swelling of your face, mouth, tongue, lips, gums, neck, or throat (angioedema)
• plan to father a child. Animal studies have shown that pregabalin, the active ingredient in LYRICA, made male animals less fertile and caused sperm to change. Also, in animal studies, birth defects were seen in the offspring (babies) of male animals treated with pregabalin. It is not known if these problems can happen in people who take LYRICA.
• are pregnant or plan to become pregnant. It is not known if LYRICA will harm your unborn baby. You and your healthcare provider will decide if you should take LYRICA while you are pregnant.
  • If you become pregnant while taking LYRICA, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. Information about the registry can also be found at the website, http://www.aedpregnancyregistry.org/.
• are breastfeeding or plan to breastfeed. LYRICA passes into your breast milk. It is not known if Lyrica can harm your baby.

Talk to your healthcare provider about the best way to feed your baby if you take LYRICA. Breastfeeding is not recommended while taking LYRICA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins or herbal supplements. LYRICA and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take:

• angiotensin converting enzyme (ACE) inhibitors, which are used to treat many conditions, including high blood pressure. You may have a higher chance for swelling and hives if these medicines are taken with LYRICA.
• Avandia (rosiglitazone) or Actos (pioglitazone) for diabetes. You may have a higher chance of weight gain or swelling of your hands or feet if these medicines are taken with LYRICA.
• any narcotic pain medicine (such as oxycodone), tranquilizers or medicines for anxiety (such as lorazepam). You may have a higher chance for dizziness and sleepiness if these medicines are taken with LYRICA.
• any medicines that make you sleepy Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist each time you get a new medicine. Do not start a new medicine without talking with your healthcare provider.

How should I take LYRICA?

• Take LYRICA exactly as prescribed. Your healthcare provider will tell you how much LYRICA to take and when to take it.
• Take LYRICA at the same times each day.
• LYRICA may be taken with or without food.
• Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.
• Do not stop taking LYRICA without talking to your healthcare provider. If you stop taking LYRICA suddenly you may have headaches, nausea, diarrhea, trouble sleeping, increased sweating, or you may feel anxious. If you have epilepsy and you stop taking LYRICA suddenly, you may have seizures more often. Talk with your healthcare provider about how to stop LYRICA slowly.
• If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take two doses at the same time.
• If you take too much LYRICA, call your healthcare provider or poison control center, or go to the nearest emergency room right away.

What should I avoid while taking LYRICA?

• Do not drive a car, work with machines, or do other dangerous activities until you know how LYRICA affects you.
• Do not drink alcohol while taking LYRICA. LYRICA and alcohol can affect each other and increase side effects such as sleepiness and dizziness.

What are the possible side effects of LYRICA?

LYRICA may cause serious side effects, including:

• See “What is the most important information I should know about LYRICA?”
• Muscle problems, muscle pain, soreness, or weakness. If you have these symptoms, especially if you feel sick and have a fever, tell your healthcare provider right away.
• Problems with your eyesight, including blurry vision. Call your healthcare provider if you have any changes in your eyesight.
• Weight gain. If you have diabetes, weight gain may affect the management of your diabetes. Weight gain can also be a serious problem for people with heart problems.
• Feeling “high”

The most common side effects of LYRICA are:

• dizziness
• trouble concentrating
• blurry vision
• swelling of hands and feet
• weight gain
• dry mouth
• sleepiness

LYRICA caused skin sores in animal studies. Skin sores did not happen in studies in people. If you have diabetes, you should pay attention to your skin while taking LYRICA and tell your healthcare provider about any sores or skin problems.

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the possible side effects of LYRICA. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store LYRICA?

• Store LYRICA capsules and oral solution at room temperature, 68oF to 77°F (20oC to 25°C) in its original package.
• Safely throw away any LYRICA that is out of date or no longer needed.

Keep LYRICA and all medicines out of the reach of children.

General information about the safe and effective use of LYRICA

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use LYRICA for a condition for which it was not prescribed. Do not give LYRICA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about LYRICA that is written for health professionals.

You can also visit the LYRICA website at www.LYRICA.com or call 1-866-459-7422 (1-866-4LYRICA).

What are the ingredients in LYRICA?

Active ingredient: pregabalin

Inactive ingredients:

LYRICA capsules: lactose monohydrate, cornstarch, talc Capsule shell: gelatin and titanium dioxide; Orange capsule shell: red iron oxide; White capsule shell: sodium lauryl sulfate, colloidal silicon dioxide. Colloidal silicon dioxide is a manufacturing aid that may or may not be present in the capsule shells.

Imprinting ink: shellac, black iron oxide, propylene glycol, potassium hydroxide.

LYRICA oral solution: methylparaben, propylparaben, monobasic sodium phosphate anhydrous, dibasic sodium phosphate anhydrous, sucralose, artificial strawberry #11545 and purified water. LAB-0299-13.2

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Pregabalin and other medicines may affect each other. Always check with your doctor before starting or stopping any medicines. Especially tell your doctor if you take:

• 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)
• narcotic pain medications, including oxycodone (OxyContin, in Percocet, others)
• sedatives
• sleeping pills
• tranquilizers

This is not a complete list of pregabalin drug interactions. Ask your doctor or pharmacist for more information.

Take pregabalin exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

The recommended dosage varies depending upon the patient's kidney function (creatinine clearance) and the medical condition being treated. Initial dosages are often 150 mg per day in divided doses (smaller doses taken two or three times daily) and are gradually increased to a maximum dose of 600 mg per day.

Pregabalin is an anti-epileptic drug, also called an anticonvulsant. It works by slowing down impulses in the brain that cause seizures. Pregabalin also affects chemicals in the brain that send pain signals across the nervous system.

Pregabalin is used to control seizures and to treat fibromyalgia. It is also used to treat pain caused by nerve damage in people with diabetes (diabetic neuropathy), herpes zoster (post-herpetic neuralgia), or spinal cord injury.

Pregabalin may also be used for purposes not listed in this medication guide.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take the medicine at the same time each day.

You may take pregabalin with or without food.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not stop using pregabalin suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using this medicine.

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

Wear a medical alert tag or carry an ID card stating that you take pregabalin. Any medical care provider who treats you should know that you take seizure medication.

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

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Taking pregabalin with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking a sleeping pill, narcotic (opioid) medication, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• oral diabetes medicine--pioglitazone, rosiglitazone; or

• an ACE inhibitor--benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.

This list is not complete. Other drugs may interact with pregabalin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Anticonvulsant; structurally related to the inhibitory CNS neurotransmitter GABA; also possesses analgesic activity.1 2 3 5 6 8 18

It is very important that your doctor check your progress at regular visits, especially for the first few months you take pregabalin. This is necessary to allow dose adjustments and to check for any unwanted effects.

Stop using pregabalin and call your doctor right away if you have swelling of the face, eyes, lips, gums, or tongue, or problems with swallowing or breathing. Tell your doctor if you have hives or a skin rash, redness, or blisters while you are using pregabalin. You may be having a severe allergic reaction or a condition called angioedema.

pregabalin will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; medicines for seizures (eg, barbiturates); muscle relaxants; or anesthetics, including some dental anesthetics. Check with your medical doctor or dentist before taking any of these while you are taking pregabalin.

pregabalin may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts or to become more depressed. If you or your caregiver notice any of these side effects, tell your doctor right away.

Pregabalin may cause blurred vision, double vision, clumsiness, unsteadiness, dizziness, drowsiness, or trouble with thinking. Make sure you know how you react to pregabalin before you drive, use machines, or do anything else that could be dangerous if you are not alert, well-coordinated, or able to think or see well. If these side effects are especially bothersome, check with your doctor.

pregabalin may cause you to have extra fluid or to gain weight. This may cause problems for people with heart failure. If these side effects are bothersome, check with your doctor.

Do not suddenly stop taking pregabalin without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. Stopping the medicine suddenly may cause seizures or side effects such as dizziness, diarrhea, nausea, headaches, vomiting, irritability, trouble with sleeping, nightmares, or tingling feelings.

Call your doctor if you have any unexplained muscle pain, tenderness, or weakness, especially with a fever. These may be symptoms of a serious muscle problem called myopathy.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

(pre GAB a lin)

Applies to pregabalin: oral capsule, oral solution

Along with its needed effects, pregabalin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking pregabalin:

• Difficult or labored breathing
• shortness of breath
• tightness in the chest

• Blistering, peeling, or loosening of the skin
• chills
• cough
• diarrhea
• difficulty with swallowing
• dizziness
• fast heartbeat
• hives
• itching
• joint or muscle pain
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• skin rash
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• unusual tiredness or weakness

Some side effects of pregabalin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Accidental injury
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• burning, tingling, numbness or pain in the hands, arms, feet, or legs
• change in walking and balance
• clumsiness
• confusion
• delusions
• dementia
• difficulty having a bowel movement (stool)
• difficulty with speaking
• double vision
• dry mouth
• fever
• headache
• hoarseness
• increased appetite
• lack of coordination
• loss of memory
• lower back or side pain
• painful or difficult urination
• problems with memory
• rapid weight gain
• seeing double
• sensation of pins and needles
• shakiness and unsteady walk
• sleepiness or unusual drowsiness
• stabbing pain
• swelling
• tingling of the hands or feet
• trembling, or other problems with muscle control or coordination
• unusual weight gain or loss

• Anxiety
• bloated or full feeling
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• cold sweats
• coma
• cool, pale skin
• cough producing mucus
• decrease or change in vision
• depression
• excess air or gas in the stomach or intestines
• eye disorder
• false or unusual sense of well-being
• general feeling of discomfort or illness
• increased hunger
• joint pain
• loss of appetite
• loss of bladder control
• loss of strength or energy
• muscle aches and pains
• muscle twitching or jerking
• muscle weakness
• nausea
• nervousness
• nightmares
• noisy breathing
• pain
• passing gas
• rhythmic movement of the muscles
• runny nose
• seizures
• shivering
• slurred speech
• sweating
• trouble sleeping
• twitching
• uncontrolled eye movements
• vomiting

-Initial dose: 50 mg orally 3 times a day
-Titration: The dose may be increased to 100 mg orally 3 times a day within 1 week based on efficacy and tolerability
-Maximum dose: 100 mg orally 3 times a day in patients with a creatinine clearance of at least 60 mL/min

Comment:
-This drug may be taken with or without food.

Use: Management of neuropathic pain associated with diabetic peripheral neuropathy

• Pregabalin exhibits both nerve-pain relieving and anticonvulsant activity.
• Used as an anticonvulsant in addition to other anticonvulsants for the treatment of partial onset seizures.
• May be used in the treatment of neuropathic pain associated with diabetes or spinal cord injury.
• Indicated for the treatment of fibromyalgia and postherpetic neuralgia (nerve pain that occurs following shingles).
• May be used off-label for generalized anxiety disorder, hot flashes, restless legs syndrome and social anxiety disorder.
• The dosage of pregabalin does not need adjusting in people with liver disease.

Pregabalin is used in the treatment of nerve pain and also as an anticonvulsant. Drowsiness or dizziness are common side effects.