Patients who do not experience sufficient pain relief following 2 to 3 weeks of treatment with 300 mg per day, and who are able to tolerate LYRICA, may be treated. 2 DOSAGE AND ADMINISTRATION 2.1 Important Administration Instructions. LYRICA is given orally with or without food. 2.2 Neuropathic Pain Associated with Diabetic Peripheral Neuropathy in Adults. 2.3 Postherpetic Neuralgia in Adults. The recommended dose of LYRICA is 75 to 150 mg two times.
MethodsThis was a pooled analysis of 6 flexible-dose clinical trials of pregabalin in patients with neuropathic pain (diabetic peripheral neuropathy, peripheral herpetic neuralgia, posttraumatic pain, or postsurgical pain). Patients were divided into “dose pathway” groups based on their weekly pregabalin dose from the start of their trial to the first week of their maintenance phase.
These were: 150 mg/day only; 150 to 300 mg/day; 150 to 300 to 450 mg/day; 150 to 300 to 450 to 600 mg/day; 150 to 300 to 600 mg/day; 300 to 600 mg/day. Pain outcomes assessed for each group at each new dose were proportion of 30% and 50% responders (≥30% or ≥50% reduction in mean pain score from baseline) and mean change in pain score. Percent change in mean pain score from baseline was assessed using a marginal structural model. ResultsSeven hundred and sixty-one patients treated with flexible-dose pregabalin were included in the analysis. For each dose pathway group, there was a notably greater proportion of 30% and 50% responders and change in pain score, at each escalating dose.
As assessed by the marginal structural model, higher doses of pregabalin were estimated to result in a significantly greater change in mean pain score at each week. This dose response with flexible-dose pregabalin was consistent with that previously observed with fixed-dose pregabalin. IntroductionNeuropathic pain, defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system” is a common chronic pain condition. Source dataThis analysis included all Pfizer-sponsored studies of pregabalin completed at the time the analysis started that met the following criteria: randomized, parallel, placebo-controlled; conducted in patients with neuropathic pain; and included a treatment arm of flexible-dose pregabalin (150 to 600 mg/day). Only Pfizer-sponsored studies were included as patient-level data were required for the analysis.
A total of 6 trials met these criteria. A 12-week trial conducted in 406 patients with DPN, A0081030 (: ). A 4-week trial conducted in 269 patients with PHN, A0081004. A 12-week trial conducted in 338 patients with either DPN or PHN, 1008–1155. An 8-week trial conducted in 308 patients with either DPN or PHN, A0081081. An 8-week trial conducted in 254 patients with posttraumatic or postsurgical (PT/PS) pain, A0081064.
An 8-week trial conducted in 240 patients with DPN, PHN, or PT/PS, A0081037. Some historical trials are not recorded at.The trials were conducted between July 2001 and May 2008 and included patients from Asia, Europe, the Middle East, and North and South America. The primary efficacy outcome in each study was the change in mean pain score at endpoint compared with placebo. Mean pain score was the mean score over the past 7 days as recorded by patients in a daily pain diary and measured using an 11-point numeric rating scale scored from 0 (no pain) to 10 (worst possible pain).Data on the pain response to fixed-dose pregabalin were taken from all Pfizer-sponsored, randomized, placebo-controlled trials of pregabalin in patients with neuropathic pain.
This was a total of 27 trials: 1008–1014, 1008–1029, 1008–1030, 1008–1040, 1008–1045, 1008–1125, 1008–1127, 1008–1131, 1008–1149, 1008–1155, 1008–1196, A0081004 (ClinicalTrials. Gov: ), A0081030 , A0081037 , A0081060 , A0081064 , A0081066, A0081071 , A0081081 , A0081107 , A0081120 , A0081163 , A0081244 , A0081265 , A0081268 , A0081269 , and A0081276. Some historical trials are not recorded at.The protocol for each trial adhered to the International Ethical Guidelines for Biomedical Research Involving Human Subjects, the International Conference on Harmonisation Good Clinical Practice guidelines, and the Helsinki Declaration. All trials were approved by the appropriate independent ethics committee and all patients provided written informed consent. Dose pathway groupsTo be included in this analysis, patients had to have ≥80% compliance on the study drug (calculated by total number of days on a valid dose/duration of treatment), to have remained in their study for at least 28 days, and to have been receiving a stable dose of pregabalin for at least 4 days. Patients were grouped into dose pathways based on the pattern of their pregabalin dose at each week during titration phase and up to 1 week of their maintenance phase. The dose pathway groups were: 150 mg/day only; 150 to 300 mg/day; 150 to 300 to 450 mg/day; 150 to 300 to 450 to 600 mg/day; 150 to 300 to 600 mg/day; and 300 to 600 mg/day.
Each patient was included in a single-dose pathway group. Patients who decreased their dose at any visit or who did not remain at the particular dose level for at least 4 days were not included in a dose pathway group.
Statistical analysisDescriptive statistics were used to describe outcomes in treatment-compliant and non-compliant patients for each dose pathway. Assessed outcomes included: proportion of 30% responders (patients with ≥30% reduction in mean pain score from baseline); proportion of 50% responders (patients with ≥50% reduction in mean pain score from baseline); and mean change in pain score at each new dose. Patient populationA total of 889 patients were treated with flexible-dose pregabalin; 761 of which met the inclusion criteria (≥80% compliance on pregabalin, had remained in their study for ≥28 days, and receiving a stable dose of pregabalin for ≥4 days) and were included in the descriptive analysis.
Of these, 717 could be grouped into one of the six established dose response pathways. The demographic characteristics and baseline clinical characteristics of patients were broadly similar regardless of treatment compliance. Improvement in pain outcomes in each dose pathwayCumulative assessment of the proportion of 30% and 50% pain responders for each dose pathway showed that across every dose pathway, there was recruitment of new pain responders (30% or 50%) at each new and higher dose of pregabalin. Shows the number (and proportion) of 30% responders at each dose limited to only those patients who were non-responders at the previous dose in their dose pathway (i.e., non-cumulative data). For example, in the 150 to 300 mg/day dose pathway, 100 (of 146) patients were non-responders at 150 mg/day. When these patients were escalated to 300 mg/day, a further 43 (of the 100 non-responding) patients were responders.
An equivalent pattern was observed with 50% responders. These data demonstrate that for every dose pathway, previously non-responsive patients would become 30% or 50% responders with every increase in pregabalin dose. BNumber (percentage) of patients who were 50% responders at that dose.The change in pain score from baseline for each dose pathway indicated that patients in the shorter dose pathways (i.e., those who remained on 150 mg/day or only escalated to 300 mg/day) had a notable larger change in pain score with pregabalin 150 mg/day (and 300 mg/day) than did those patients who subsequently went on to be escalated to higher doses. This finding reflects the fact that patients with a greater response at lower doses were less likely to be escalated to a higher dose.
At the same time, for those patients who were escalated to a higher dose, there was a notably greater change in pain score at each escalating dose. Dose150 mg/day150 to 300 mg/day150 to 300 to 450 mg/day150 to 300 to 450 to 600 mg/day150 to 300 to 600 mg/day300 to 600 mg/dayn aChange bn aChange bn aChange bn aChange bn aChange bn aChange bBased on 30% pain responders population150 mg/day67−1.92146−1.33144−0.72298−0.5546−0.50300 mg/day100−1.56122−1.18272−0.8639−0.4616−2.19450 mg/day86−1.34231−1.02600 mg/day188−0.9736−0.628−1.90Based on 50% pain responders population150 mg/day67−1.92146−1.33144−0.72298−0.5546−0.50300 mg/day131−2.00136−1.32290−0.9845−0.7716−2.19450 mg/day118−1.79277−1.35600 mg/day252−1.5041−1.0213−2.45.
Weighted estimation of change in pain score for each doseAs assessed by MSM, higher doses of pregabalin were estimated to result in a significantly greater change in mean pain score at each week of assessment. Restricting the analysis to only those patients with ≥80% compliance with pregabalin resulted in similar results (not shown). This was also supported by a comparison of the weighted MSM analysis with an unweighted estimate of the change in mean pain score, with each analysis showing similar results (not shown). Estimated change in pain score from baseline by marginal structural model showing that increasing doses of pregabalin result in a greater reduction in pain score.Notes: All doses of pregabalin significantly ( P300 mg/day at each week. There was no significant difference observed between 450 mg/day and 600 mg/day at any week.Direct comparison of the MSM-estimated change with flexible-dose pregabalin with the estimated change in mean pain score from baseline with data from fixed-dose clinical trials of pregabalin (a total of 3128 patients; 516 receiving pregabalin 150 mg/day, 1679 receiving pregabalin 300 mg/day, and 933 receiving pregabalin 600 mg/day) demonstrated a similar dose-response pattern for each dose of pregabalin. DiscussionPregabalin is recommended as a treatment for diverse neuropathic pain conditions,– where it is advised that it be carefully escalated to the optimal dose., In the USA, the maximum approved dose of pregabalin is 300 mg/day for DPN and 600 mg/day for PHN, while in Europe it is 600 mg/day for all neuropathic pain.
Despite this, many patients may not receive the most effective dose of pregabalin, with a recent drug utilization study in the UK indicating that the approximate median prescribed dose of pregabalin for neuropathic pain was only 150 mg/day. This analysis provides evidence that new patients will tend to respond with every increase in pregabalin dose.Neuropathic pain can be challenging to treat effectively.
While there are a number of treatment options, not all are effective in all patients. For instance, data on the efficacy of pregabalin in patients with lower back pain are inconsistent., In a randomized withdrawal trial, pregabalin was not shown to be effective in patients with chronic lumbosacral radiculopathy. Even for those conditions where its efficacy is well established, many patients will not respond to treatment with pregabalin. As physicians are advised to ensure that effective and tolerable treatment for neuropathic pain is initiated as soon as possible, it is important to ascertain quickly if a treatment is ineffective so that other options can be tested. In these circumstances, it may be understandable why the time is not taken to escalate some patients to a higher, efficacious dose of pregabalin. However, of the 701 patients in this analysis who took the 150 mg/day dosing, 136 (19.4%) responded at that dose.
Of those who continued to higher doses, 231 (33.0%) responded at a higher dose. These data do not correct for the tendency for higher doses to be used when patients have inadequate response at a lower dose.
The MSM analyses make some correction for this tendency in dose escalation and indicate that it can be worthwhile to persist with pregabalin until the dose that delivers optimal analgesia and tolerable side effects is utilized.Physicians may be reluctant to escalate the dose of pregabalin due to concerns about adverse events. A previous analysis described the incidence of common adverse events with each dose of pregabalin. In that analysis, the incidence of most adverse events was higher with higher fixed doses (450 or 600 mg/day) of pregabalin.
However, the incidence of adverse events with flexible-dose pregabalin was lower than with any fixed dose 150 mg/day. In addition, most adverse events emerged soon after the start of treatment and resolved within 1–2 weeks. It was advised that potential adverse events with pregabalin be discussed with patients, before and during treatment, as greater awareness of what to expect could help manage expectations. Together with the data reported here, this suggests that communication and careful dose titration could result in improved pain outcomes for patients.Fixed dose studies have previously demonstrated a clear dose response with pregabalin., In these studies, patients were assigned to a specific fixed dose prior to treatment with the dose response being shown for a population of patients. Here, for the first time, this analysis shows that this dose response also exists for flexible-dose pregabalin, with individual patients being shown to respond to increasing doses. This dose response was shown to be broadly equivalent in the direct comparison between flexible- and fixed-dose pregabalin shown in. This may suggest that in the future, some initial fixed-dose clinical trials could theoretically be replaced with flexible-dosing trials that would allow for fewer treatment arms.
However, this would require additional data, and confirmation with other treatments and in other patient groups before it could be considered. While a previous analysis also used a MSM to evaluate dose-response in inflexible-dose trials of an antipsychotic, the analysis did not directly compare this with data from fixed-dose trials.
We are not aware of any comparable analysis for any treatment for neurological pain. LimitationThe descriptive part of this analysis was limited to those patients who were ≥80% compliant with treatment. As would be expected, there was a notably lower rate of efficacy among those patients who were.
. Hypersensitivity (allergic) reaction warning: This drug can cause serious allergic reactions. These include trouble breathing, shortness of breath, and rash, and blisters on your skin.
If you have any of these symptoms, stop taking this drug and seek medical help right away. Suicidal thinking and behavior warning: This drug can increase your risk of having and behavior. Talk to your doctor right away if you have any unusual changes in your mood or behavior, new or worsening, or thoughts of harming yourself. Dizziness and drowsiness warning: This drug can cause dizziness, drowsiness, and blurry vision. It may affect your ability to think, see, or move. You shouldn’t drive, use machinery, or do other tasks that require alertness until you know how this drug affects you.
Misuse warning: Use of this drug can lead to misuse. Your risk may be greater if you have a history of drug misuse. Pregabalin is a prescription drug. It comes in three forms: a capsule, a solution, and an extended-release tablet. All forms are taken by mouth.Pregabalin oral capsule is available as the brand-name drug Lyrica. It isn’t available as a generic drug.Pregabalin oral capsule may be used as part of a combination therapy. This means you may need to take it with other medications.Pregabalin is a.
Your doctor will closely monitor your use of this drug. Why it’s usedPregabalin oral capsule is used to treat:. caused by damaged nerves due to, or. (pain all over your body). when taken with other seizure drugsHow it worksPregabalin belongs to a class of drugs called anticonvulsants. A class of drugs is a group of medications that work in a similar way.
These drugs are often used to treat similar conditions.It isn’t known exactly how pregabalin works. It’s believed to work by calming the damaged or overactive nerves in your body that may cause pain or seizures. Pregabalin oral capsule can cause dizziness, sleepiness, and blurry vision.
It may affect your ability to think, see, or move. You shouldn’t drive, use machinery, or do other tasks that require alertness until you know how this drug affects you.Pregabalin can also cause other side effects. More common side effectsThe more common side effects of pregabalin can include:.
dizziness. sleepiness. trouble concentrating. blurry vision. weight gain.
swelling of your hands or feetIf these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist. Serious side effectsCall your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:. Serious allergic reactions.
These reactions may be life-threatening. Symptoms can include:. swelling of your face, mouth, lips, gums, tongue, throat, or neck. trouble breathing. rash, hives (raised bumps), or blisters.
Suicidal thoughts or actions. Symptoms can include:. thoughts of suicide or dying. attempts to commit suicide.
new or worsened depression or. feeling agitated or restless. trouble sleeping. new or worsened irritability. acting aggressive, angry, or violent. acting on dangerous impulses.
mania (an extreme increase in activity and talking). other unusual changes in behavior or mood. Heart problems.
Symptoms can include:. swelling of your hands, legs, or feet. chest pain. Dizziness and sleepinessDisclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice.
Always discuss possible side effects with a healthcare provider who knows your medical history. Pregabalin oral capsule can interact with other medications, or herbs you may be taking. An interaction is when a substance changes the way a drug works.
This can be harmful or prevent the drug from working well.To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.Examples of drugs that can cause interactions with pregabalin are listed below. Interactions that cause increased side effectsTaking pregabalin with certain medications may cause more side effects. These drugs include:. Diabetes drugs, such as rosiglitazone and pioglitazone. Taking these drugs with pregabalin may cause weight gain or swelling of your hands or feet.
If you have heart problems, taking these drugs together can increase your risk of. Narcotic pain drugs, such as oxycodone. Taking these drugs with pregabalin may cause dizziness and sleepiness. Tranquilizers (drugs that make you sleepy) or drugs for anxiety, such as lorazepam. Taking these drugs with pregabalin may cause dizziness and sleepiness. Blood pressure drugs, such as captopril, enalapril, or lisinopril.
Taking these drugs with pregabalin may cause swelling and hives.Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.
This drug comes with several warnings. Allergy warningThis drug can cause a severe allergic reaction. Symptoms can include:. trouble breathing. swelling of your face, mouth, lips, gums, neck, throat, or tongue.
rash, hives (raised bumps), or blistersIf you develop these symptoms, call 911 or go to the nearest emergency room.Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death). Alcohol interaction warningThe use of drinks that contain alcohol can increase the risk of drowsiness and dizziness from pregabalin. You shouldn’t drink alcohol while taking this drug.
If you drink alcohol, talk to your doctor. Warnings for people with certain health conditionsFor people with kidney problems: If you have kidney problems or a history of kidney disease, you may not be able to clear this drug from your body well. This may increase the levels of this drug and cause more side effects. Your doctor may give you a lower dosage to help avoid side effects.For people with heart problems: Ask your doctor whether this drug is safe for you if you have heart problems, such as moderate to severe heart failure.
This drug can make your condition worse. Symptoms of worsening heart problems can include swelling in your arms, legs, or feet, weight gain, and (swelling) in your body.For people with depression or mental health issues: If you have depression or other or behavioral problems, this drug may increase your risk of suicidal thoughts and behaviors. You and your family should watch for new or worsened depression, unusual changes in your mood or behavior, or thoughts of harming yourself.For people with a history of drug or alcohol misuse: Let your doctor know if you have misused prescription or street drugs or alcohol in the past. Pregabalin is a controlled substance and its use can lead to misuse. Warnings for other groupsFor pregnant women: Talk to your doctor if you’re pregnant or planning to become pregnant.
This drug should only be used if the potential benefit justifies the potential risk. Animal studies have shown that high doses of pregabalin increased the risk of negative effects to the fetus.If you become pregnant while taking this drug, talk to your healthcare provider about registering with the North American Antiepileptic Drug Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs used during pregnancy.For women who are breastfeeding: Pregabalin passes into breast milk in small amounts. Therefore, it may cause side effects in a child who is breastfed.Talk to your doctor if you breastfeed your child.
You may need to decide whether to stop breastfeeding or stop taking this medication.For men with plans to father a child: Animal studies have shown that this drug caused sperm to change and made male animals less fertile. Also, birth defects were seen in the babies of male animals who were treated with this drug. It isn’t known if these problems can happen in people who take this drug.For seniors: Your kidneys may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time. This raises your risk of side effects.For children: This drug hasn’t been studied in children. It shouldn’t be used in children younger than 18 years.
All possible dosages and drug forms may not be included here. Pregabalin oral capsule is used for long-term treatment. It comes with serious risks if you don’t take it as prescribed.If you stop taking the drug suddenly or don’t take it at all: Your pain or seizures won’t go away or may get worse.If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely. For this drug to work well, a certain amount needs to be in your body at all times.If you take too much: You could have dangerous levels of the drug in your body. Symptoms may include:. dizziness. drowsiness.
loss of control of body movements. tremors (constant shaking). (forgetfulness or loss of memory).
trouble speaking. nervousness.
twitching.If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.What to do if you miss a dose: Take your dose as soon as you remember. But if you remember just a few hours before your next scheduled dose, take only one dose. Never try to catch up by taking two doses at once. This could result in dangerous side effects.How to tell if the drug is working: For peripheral, and nerve pain caused by a spinal cord injury: You should feel less burning, tingling, or numbing pain.For fibromyalgia: You should feel less pain all over your body.For seizures: Your seizures should be better controlled.
Keep these considerations in mind if your doctor prescribes pregabalin for you. General. You can take this drug with or without food.
Take this drug at the time(s) recommended by your doctor.Storage. Store this drug at room temperature. Keep it between 59°F and 86°F (15°C and 30°C). Keep this drug away from light. Don’t store this medication in moist or damp areas, such as bathrooms.RefillsA prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.
TravelWhen traveling with your medication:. Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag. Don’t worry about airport X-ray machines. They can’t harm your medication. You may need to show airport staff the pharmacy label for your medication.
Always carry the original prescription-labeled container with you. Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.Clinical monitoringYou and your doctor should monitor certain health issues. This can help make sure you stay safe while you take this drug. These issues include your:. Kidney function: Your doctor may do blood tests to check how well your kidneys are working. If your kidneys aren’t working well, your doctor may lower your dosage of this drug.
Mental and behavioral health: You and your doctor should watch for any unusual changes in your behavior and mood. This drug can cause new mental health and behavior problems. It can also worsen problems you already have.AvailabilityNot every pharmacy stocks this drug. When filling your prescription, be sure to call ahead to make sure your pharmacy carries it. Prior authorizationMany insurance companies require a prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription. There are other drugs available to treat your condition.
Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.
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