Maxgalin

Pregabalin.

Each capsule contains: Pregabalin 50 mg, 75 mg, or 150 mg.

Pharmacology: Pharmacodynamics: Pregabalin, is a gamma-aminobutyric acid analogue.
Mechanism of Action: Pregabalin binds with high affinity to the alpha₂-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically-modified mice and with compounds structurally related to pregabalin suggest that binding to the alpha₂-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animal models.
While pregabalin is a structural derivative of the inhibitory neurotransmitter gammaaminobutyric acid (GABA), it does not bind directly to GABA_A, GABA_B, or benzodiazepine receptors, does not augment GABA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation.
Pharmacokinetics: Pregabalin is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours. Following oral administration of pregabalin capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Pregabalin oral bioavailability is >90% and is independent of dose. Following single (25 to 300 mg) and multiple dose (75 to 900 mg/day) administration, maximum plasma concentrations (C_max) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.
The rate of pregabalin absorption is decreased when given with food, resulting in a decrease in C_max of approximately 25% to 30% and an increase in T_max to approximately 3 hours. However, administration of pregabalin with food has no clinically relevant effect on the total absorption of pregabalin. Therefore, pregabalin can be taken with or without food. Pregabalin does not bind to plasma proteins. The apparent volume of distribution of pregabalin following oral administration is approximately 0.5 L/kg.

Maxgalin is indicated: For the treatment of peripheral neuropathic pain in adults.
As adjunctive therapy for adult patients with partial onset seizures.

Pregabalin is given orally with or without food. When discontinuing pregabalin, taper gradually over a minimum of 1 week.
Neuropathic pain: The maximum recommended dose of pregabalin is 100 mg three times a day (300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Dosing should begin at 50 mg three times a day (150 mg/day) and may be increased to 300 mg/day within 1 week based on efficacy and tolerability. Because pregabalin is eliminated primarily by renal excretion, the dose should be adjusted for patients with reduced renal function.
Although pregabalin was also studied at 600 mg/day, there is no evidence that this dose confers additional significant benefit and this dose was less well tolerated. In view of the dose dependent adverse effects, treatment with doses above 300 mg/day are not recommended.
Epilepsy: Pregabalin at doses of 150 to 600 mg/day has been shown to be effective as adjunctive therapy in the treatment of partial onset seizures in adults. The total daily dose should be divided and given either two or three times daily. Both the efficacy and adverse event profiles of pregabalin have been shown to be dose related. In general, it is recommended that patients be started on a total daily dose no greater than 150 mg/day (75 mg two times a day, or 50 mg three times a day). Based on individual patient response and tolerability, the dose may be increased to a maximum dose of 600 mg/day.
The effect of dose escalation rate on the tolerability of pregabalin has not been formally studied.
The efficacy of add on pregabalin in patients taking gabapentin has not been evaluated in controlled trials.
Consequently, dosing recommendations for the use of pregabalin with gabapentin cannot be offered.
Patients with Renal Impairment: In view of dose dependent adverse events and since pregabalin is eliminated primarily by renal excretion, the dose should be adjusted in patients with reduced renal function. Dosage adjustment in patients with renal impairment should be based on CL_cr , as indicated in following table. To use this dosing table, an estimate of the patient's CL_cr in mL/min is needed. CL_cr in mL/min may be estimated from serum creatinine (mg/dL) determination using the Cockcroft and Gault equation: See Equation.

Click on icon to see table/diagram/image

For patients undergoing hemodialysis, pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose adjustment, a supplemental dose should be given immediately following every 4-hour hemodialysis treatment as shown in table below: See Table.

Click on icon to see table/diagram/image

Elderly: Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearanceis consistent with age related decreases in Cl_cr.
No overall differences in safety and efficacy were observed between these patients and younger patients. Even though the incidence of adverse events did not increase with age, greater sensitivity of some older individuals cannot be ruled out. Pregabalin is known to be substantially excreted by the kidney, and the risk of toxic reactions to pregabalin may be greater in patients with impaired renal function.
Because pregabalin is eliminated primarily by renal excretion, the dose should be adjusted for elderly patients with renal impairment.
Pediatric use: The safety and efficacy of pregabalin in pediatric patients have not been established.

There is limited experience with overdose of pregabalin. The highest reported accidental overdose of pregabalin during the clinical development program was 8000 mg, and there were no notable clinical consequences. The types of adverse events experienced by patients exposed to higher doses (>900 mg) were not clinically different from those of patients administered recommended doses of pregabalin.
There is no specific antidote for overdose with pregabalin. If indicated, elimination of unabsorbed drug may be attempted by emesis or gastric lavage; usual precautions should be observed to maintain the airway. General supportive care of the patient is indicated including monitoring of vital signs and observation of the clinical status of the patient.
Although hemodialysis has not been performed in the few known cases of overdose, it may be indicated by the patients clinical state or in patients with significant renal impairment. Standard hemodialysis procedures result in significant clearance of pregabalin.

Known hypersensitivity to pregabalin or any component of the formulation.

As with all AEDs, pregabalin should be withdrawn gradually to minimize the potential of increased seizure frequency in patients with seizure disorders. Following abrupt or rapid discontinuation of pregabalin, some patients reported symptoms including insomnia, nausea, headache, diarrhea, flu syndrome, nervousness, depression, pain, sweating and dizziness. If pregabalin is discontinued this should be done gradually over a minimum of 1 week. Concerning discontinuation of long-term treatment of pregabalin there are no data of the incidence and severity of withdrawal symptoms in relation to duration of use and dosage of pregabalin.
There are insufficient data for the withdrawal of concomitant antiepileptic medicinal products, once seizure control with pregabalin in the add-on situation has been reached.
Pregabalin causes dizziness and somnolence. Patients should be informed that pregabalin-related dizziness and somnolence may impair their ability to perform tasks such as driving or operating machinery.
Pregabalin treatment caused weight gain and edema, primarily described as peripheral edema. As the thiazolidinedione class of antidiabetic drugs can cause weight gain and/or fluid retention, possible exacerbating or leading to heart failure, care should be taken when coadministering pregabalin and these agents. Therefore, dosage adjustment of these antidiabetics may be required.
Because there are limited data on congestive heart failure patients with New York Heart Association (NYHA) Class III or IV cardiac status, pregabalin should be used with caution in these patients.
Pregabalin treatment was associated with creatine kinase elevations. Prescribers should instruct patients to promptly report unexplained muscle pain, tenderness, or weakness, particularly if these muscle symptoms are accompanied by malaise or fever. Pregabalin treatment should be discontinued if myopathy is diagnosed or suspected or if markedly elevated creatine kinase levels occur.
Pregabalin treatment was associated with decrease in platelet count and mild PR interval prolongation.
Patients should be counseled that pregabalin may cause visual disturbances. Patients should be informed that if changes in vision occur, they should notify their physician.
Patients who require concomitant treatment with central nervous system depressants such as opiates or benzodiazepines should be informed that they may experience additive CNS side effects, such as somnolence.
Patients should be told to avoid consuming alcohol while taking pregabalin, as pregabalin may potentiate the impairment of motor skills and sedation of alcohol.
Men being treated with pregabalin who plan to father a child should be informed of the potential risk of male-mediated teratogenicity.
Diabetic patients should be instructed to pay particular attention to skin integrity while being treated with pregabalin. Some animals treated with pregabalin developed skin ulcerations, although no increased incidence of skin lesions associated with pregabalin was observed in clinical trials.

There are no adequate and well controlled studies in pregnant women. Maxgalin should be used during pregnancy only if the potential benefit justifies the potential risk to the featus.
It is not known if pregabalin is excreted in human milk ; it is, however, present in the milk of rats. Because many drugs are excreted in human milk, and because of the potential for tumorigenicity shown for pregabalin in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The most commonly reported adverse effects with pregabalin are asthenia, accidental injury, back pain, chest pain, face edema, dry mouth, constipation, flatulence, peripheral edema, weight gain, edema, hypoglycemia, dizziness, somnolence, neuropathy, ataxia, vertigo, confusion, euphoria, incoordination, abnormal thinking, tremor, abnormal gait, amnesia, nervousness, dyspnea, blurry vision, abnormal vision, infection, headache, pain, flu syndrome, vomiting, myasthenia, speech disorder, bronchitis, diplopia, eye disorder, urinary incontinence, twitching, myoclonus, increased appetite, irritability, memory impairement, disturbance in attention, erectile dysfunction and fatigue.
Other infrequently reported adverse effects are abdominal pain, allergic reaction, fever, abscess, cellulitis, chills, malaise, neck rigidity, overdose, pelvic pain, photosensitivity reaction, suicide attempt, deep thrombophlebitis, heart failure, hypotension, postural hypotension, retinal vascular disorder, syncope, gastroenteritis, cholecystitis, cholelithiasis, colitis, dysphagia, esophagitis, gastritis, gastrointestinal hemorrhage, melena, mouth ulceration, pancreatitis, rectal hemorrhage, tongue edema, ecchymosis, anemia, eosinophilia, hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, thrombocytopenia, arthralgia, leg cramps, myalgia, arthrosis, depersonalization, hypertonia, hypesthesia, decreased libido, nystagmus, paresthesia, stupor, abnormal dreams, agitation, apathy, aphasia, circumoral paresthesia, dysarthria, hallucinations, hostility, hyperalgesia, hyperesthesia, hyperkinesia, hypotonia, increased libido, neuralgia, pruritus, alopecia, dry skin, eczema, skin ulcer, urticaria, vesiculobullous rash, conjunctivitis, otitis media, tinnitus, abnormality of accommodation, blepharitis, dry eyes, eye hemorrhage, hyperacusis, photophobia, retinal edema, taste loss, taste perversion, anorgasmia, impotence, urinary frequency, abnormal ejaculation, albuminuria, amenorrhea, dysmenorrhea, dysuria, hematuria, kidney calculus, leukorrhea, menorrhagia, metrorrhagia, nephritis, oliguria, urinary retention, anorexia, panic attack, restlessness, depression, depressed mood, mood swings, insomnia exacerbated, word finding difficulty, psychomotor hyperactivity, ageusia, dyskinesia, cognitive disorder, hyporeflexia, burning sensation, eye swelling, eye pain, asthenopia, increased lacrimation, tachycardia, flushing, hot flushes, nasal dryness, abdominal distension, gastrooesophageal reflux disease, salivary hypersecretion, sweating, joint swelling, muscle cramp, pain in limb, muscle stiffness, sexual dysfunction, thirst, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and decreased platelet count.

Since pregabalin is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (<2% of a dose recovered in urine as metabolites), does not inhibit drug metabolism in vitro, and is not bound to plasma proteins, it is unlikely to produce, or be subject to, pharmacokinetic interactions.
Accordingly, in in vivo studies no clinically relevant pharmacokinetic interactions were observed between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, or gabapentin. Population pharmacokinetic analysis indicated that oral antidiabetics, diuretics, insulin, phenobarbital, tiagabine and topiramate had no clinically significant effect on pregabalin clearance.
Coadministration of pregabalin with the oral contraceptives norethisterone and/or ethinyl oestradiol does not influence the steadystate pharmacokinetics of either substance.
Multiple oral doses of pregabalin coadministered with oxycodone, lorazepam, or ethanol did not result in clinically important effects on respiration. Pregabalin appears to the additive in the impairment of cognitive and gross motor function caused by oxycodone. Pregabalin may potentiate the effects of ethanol and lorazepam.

Do not store above 30°C, protected from light.

Anticonvulsants / Drugs for Neuropathic Pain

N02BF02 - pregabalin ; Belongs to the class of gabapentinoids. Used to relieve pain and other conditions.

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