Pregabalin: uses, appearance and warnings

Pregabalin is indicated for: • Management of neuropathic pain associated with diabetic peripheral neuropathy • Management of postherpetic neuralgia • Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older • Management of fibromyalgia • Management of neuropathic pain associated with spinal cord injury Pregabalin is indicated for: Neuropathic pain associated with diabetic peripheral neuropathy (DPN) ( 1 ) Postherpetic neuralgia (PHN) ( 1 ) Adjunctive therapy for the treatment of partial-onset seizures in patients 1 month of age and older ( 1 ) Fibromyalgia ( 1 ) Neuropathic pain associated with spinal cord injury ( 1 )

Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg. [see Description (11) and How Supplied/Storage and Handling (16) ]. Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300 mg. ( 3 )

25 mg capsules: White to off white powder filled in size"4" hard gelatin capsules, white opaque cap imprinted with 'A007' with black ink and white opaque body imprinted with "PREG 25"with black ink, available in: Bottles of 30: NDC-67877-462-30 Bottles of 90: NDC-67877-462-90 Bottles of 500: NDC-67877-462-05 Unit-Dose Blister Packages of 100 (10×10): NDC-67877-462-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-462-33 50 mg capsules: White to off white powder filled in size"3" hard gelatin capsules, white opaque cap imprinted with 'A008' with black ink and white opaque body imprinted with "PREG 50"with black ink, available in: Bottles of 30: NDC-67877-463-30 Bottles of 90: NDC-67877-463-90 Bottles of 500: NDC-67877-463-05 Unit-Dose Blister Packages of 100 (10×10): NDC-67877-463-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-463-33 75 mg capsules: White / orange hard gelatin capsules, imprinted with black ink ‘A009’ on the cap and “PREG 75” on the body; available in: Bottles of 30: NDC-67877-464-30 Bottles of 90: NDC-67877-464-90 Bottles of 500: NDC-67877-464-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-464-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-464-33 100 mg capsules: Orange hard gelatin capsules, imprinted with black ink ‘A010’ on the cap and “PREG 100” on the body; available in: Bottles of 30: NDC-67877-465-30 Bottles of 90: NDC-67877-465-90 Bottles of 500: NDC-67877-465-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-465-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-465-33 150 mg capsules: White hard gelatin capsules, imprinted with black ink ‘A011’ on the cap and “PREG 150” on the body; available in: Bottles of 30: NDC-67877-466-30 Bottles of 90: NDC-67877-466-90 Bottles of 500: NDC-67877-466-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-466-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-466-33 200 mg capsules: Light orange hard gelatin capsules, imprinted with black ink ‘A012’ on the cap and “PREG 200” on the body; available in: Bottles of 30: NDC-67877-467-30 Bottles of 90: NDC-67877-467-90 Bottles of 500: NDC-67877-467-05 Unit-Dose Blister Packages of 100(10×10): NDC-67877-467-38 Unit-Dose Blister Pack of 10 (1x10): NDC-67877-467-33 225 mg capsules : White / light orange hard gelatin capsules, imprinted with black ink ‘A013’ and “PREG 225” on the body; available in: Bottles of 30: NDC-67877-468-30 Bottles of 90: NDC-67877-468-90 Bottles of 500: NDC-67877-468-05 Unit-Dose Blister Packages of 100(10×10) …

Pregabalin is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy [see Warnings and Precautions ( 5.2 )]. Known hypersensitivity to pregabalin or any of its components. ( 4 )

Angioedema (e.g., swelling of the throat, head, and neck) can occur, and may be associated with life-threatening respiratory compromise requiring emergency treatment. Discontinue pregabalin immediately in these cases. ( 5.1 ) Hypersensitivity reactions (e.g., hives, dyspnea, and wheezing) can occur. Discontinue pregabalin immediately in these patients. ( 5.2 ) Antiepileptic drugs, including pregabalin, the active ingredient in pregabalin capsules, increase the risk of suicidal thoughts or behavior. ( 5.3 ) Abrupt or rapid discontinuation may increase the risk for seizures. Withdrawal symptoms or suicidal behavior and ideation have been observed after discontinuation. Taper pregabalin gradually over a minimum of 1 week. ( 5.4 ) Respiratory depression: May occur with pregabalin, when used with concomitant CNS depressants or in the setting of underlying respiratory impairment. Monitor patients and adjust dosage as appropriate. ( 5.5 ) Pregabalin may cause dizziness and somnolence and impair patients’ ability to drive or operate machinery. ( 5.6 ) Pregabalin may cause peripheral edema. Exercise caution when co-administering pregabalin and thiazolidinedione antidiabetic agents. ( 5.7 ) 5.1 Angioedema There have been postmarketing reports of angioedema in patients during initial and chronic treatment with pregabalin. Specific symptoms included swelling of the face, mouth (tongue, lips, and gums), and neck (throat and larynx). There were reports of life-threatening angioedema with respiratory compromise requiring emergency treatment. Discontinue pregabalin immediately in patients with these symptoms. Exercise caution when prescribing pregabalin to patients who have had a previous episode of angioedema. In addition, patients who are taking other drugs associated with angioedema (e.g., angiotensin converting enzyme inhibitors [ACE-inhibitors]) may be at increased risk of developing angioedema. 5.2 Hypersensitivity There have been postmarketing reports of hypersensitivity in patients shortly after initiation of treatment with pregabalin. Adverse reactions included skin redness, blisters, hives, rash, dyspnea, and wheezing. Discontinue pregabalin immediately in patients with these symptoms. 5.3 Suicidal Behavior and Ideation Antiepileptic drugs (AEDs), including pregabalin, the active ingredient in pregabalin capsules, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Suicidal behavior and ideation have also been reported in patients after discontinuation of pregabalin [see Warnings and Precautions ( 5.4 )]. Monitor patients treated with any AED for any indication for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono-and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs. Table 3. Risk by Indication for Antiepileptic Drugs in the Pooled Analysis Indication Placebo Patients with Events Per 1,000 Patients Drug Patients with Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients with Events Per 1,000 Patients Epilepsy 1.0 3.4 3.5 2.4 Psychiatric 5.7 8.5 1.5 2.9 Other 1.0 1.8 1.9 0.9 Total 2.4 4.3 1.8 1.9 The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Anyone considering prescribing pregabalin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. 5.4 Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation As with all antiepileptic drugs (AEDs), withdraw pregabalin gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. …

The following serious adverse reactions are described elsewhere in the labeling: Angioedema [see Warnings and Precautions ( 5.1 )] Hypersensitivity [see Warnings and Precautions ( 5.2 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.3 )] Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation [see Warnings and Precautions ( 5.4 )] Respiratory Depression [see Warnings and Precautions ( 5.5 )] Dizziness and Somnolence [see Warnings and Precautions ( 5.6 )] Peripheral Edema [see Warnings and Precautions ( 5.7 )] Weight Gain [see Warnings and Precautions ( 5.8 )] Tumorigenic Potential [see Warnings and Precautions ( 5.9 )] Ophthalmological Effects [see Warnings and Precautions ( 5.10 )] Creatine Kinase Elevations [see Warnings and Precautions ( 5.11 )] Decreased Platelet Count [see Warnings and Precautions ( 5.12 )] PR Interval Prolongation [see Warnings a …

Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro and in vivo studies showed that pregabalin is unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between pregabalin and commonly used antiepileptic drugs [see Clinical Pharmacology (12)] . …