Leptica

Pregabalin.

Pharmacology: Pharmacodynamics: Pregabalin binds with high affinity to the α₂-δ site (an auxilliary subunit of voltage-gated calcium channels) in the central nervous system (CNS).
Pharmacokinetics: Following oral administration, pregabalin is rapidly absorbed under fasting conditions and peak plasma concentration (C_max) occur within 1 hr, following both single- and multiple- dose administration. Pregabalin oral bioavailability estimated to be ≥90% and dose independent. Following repeated administration, steady-state is achieved within 24-48 hrs. However, administration of pregabalin with food has no clinically significant effect on the extent of pregabalin absorption.
Pregabalin does not bind to plasma proteins. Following oral administration, the apparent volume of distribution of pregabalin is approximately 0.56 L/kg. It has been shown to cross the blood-brain barrier in mice, rats and monkeys and has been shown to cross the placenta in rats and is present in the milk of lactating rats.
In humans, pregabalin undergoes negligible metabolism. Following a dose of radiolabeled pregabalin, approximately 98% of the administered dose was recovered in the urine as unchanged pregabalin. The N-methylated derivative of pregabalin, the major metabolite of pregabalin found in urine accounted for 0.9% of the dose.
Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life (t_½) of 6.3 hrs. Pregabalin plasma and renal clearance are directly proportional to creatinine clearance (CrCl).
Special Population: Renal Impairment and Haemodialysis: Pregabalin clearance is nearly proportional to CrCl. Reduction of pregabalin dose is required in patients with renal dysfunction and dosage supplementation following haemodialysis is necessary. Pregabalin is effectively removed from plasma by haemodialysis. Plasma pregabalin concentrations are reduced by approximately 50% following a 4-hr haemodialysis treatment. For patients on haemodialysis, dosing must be adjusted.
Elderly (>65 Years): Pregabalin oral clearance tended to decrease with increasing age. This decrease in pregabalin oral clearance is consistent with age-related decreases in CrCl. Reduction of pregabalin dose may be required in patients who have age-related compromised renal function.
Children: Pharmacokinetics of pregabalin has not been adequately studied in pediatric patients.

Neuropathic Pain: Treatment of peripheral and central neuropathic pain in adults.
Epilepsy: Adjunctive therapy in adults with partial seizures with or without secondary generalization.
Generalized Anxiety Disorder (GAD): Treatment of GAD in adults.

Neuropathic Pain: Recommended Starting Dose: 75 mg twice daily (150 mg/daily) with or without food. Based on individual patient response and tolerability, the dose may be increased to 150 mg twice daily after an interval of 3-7 days. Maximum Dose: 300 mg twice daily after an additional 7-day interval.
Epilepsy: Recommended Effective Starting Dose: 75 mg twice daily (150 mg/day) with or without food. Based on individual patient response and tolerability, the dose may be increased to 150 mg twice daily after 1 week. Maximum Dose: 300 mg twice daily after an additional week.
Generalized Anxiety Disorder: Dose Range: 150-600 mg/day given as 2 or 3 doses. The need for treatment should be reassessed regularly. Starting Dose: 150 mg/day. Based on individual patient response and tolerability, the dose may be increased to 300 mg/day after 1 week. Following an additional week the dose may be increased to 450 mg/day. Maximum Dose: 600 mg/day may be achieved after an additional week.
Discontinue of Use: In accordance with current clinical practice, if pregabalin has to be discontinued, it is recommeded that this should be done gradually over a minimum of 1 week independent of the indication.
Renal Impairment: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. As pregabalin clearance is directly proportional to CrCl, dose reduction in patients with compromised renal function must be individualized according to CrCl, as indicated in the equation determined using the following formula (see equation).


Click on icon to see table/diagram/image


Pregabalin is removed effectively from plasma by hemodialysis (50% of drug in 4 hrs). For patients receiving haemodialysis, the pregabalin daily dose should be adjusted based on renal function. In addition to the daily dose, a supplementary dose should be given immediately following every 4-hr haemodialysis treatment (see table).


Click on icon to see table/diagram/image


Hepatic Impairment: No dose adjustment is required for patients with hepatic impairment.
Use in the elderly (>65 years): Elderly patients may require a dose reduction of pregabalin due to a decreased renal function.

The most commonly reported adverse reactions observed when pregabalin was taken in overdosage included affective disorder, somnolence, confusional state, depression, agitation and restlessness.
In rare occassions, cases of coma have been reported.
Treatment of pregabalin overdosage should include general supportive measures and may induce haemodialysis if necessary.

Hypersensitivity to pregabalin or to any of the excipients of Leptica.

Lactose Intolerance: Pregabalin contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Leptica.
Diabetic Patients: In accordance with current clinical practice, some diabetic patients who gain weight on pregabalin treatment may need to adjust hypoglycaemic medication.
Hypersensitivity Reactions: There have been reports of hypersensitivity reactions, including cases of angioedema. Pregabalin should be discontinued immediately if symptoms of angioedema eg, facial, perioral or upper airway swelling occur.
Dizziness, Somnolence, Loss of Consciousness, Confusion and Mental Impairment: Pregabalin treatment has been associated with dizziness and somnolence, which could increase the occurence of accidental injury (fall) in the elderly population. There have also been reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Vision-Related Effects: Visual adverse reactions have been reported, including loss of vision, visual blurring or other changes of visual acuity, many of which were transient. Discontinuation of pregabalin may result in resolution or improvement of these visual symptoms.
Withdrawal Symptoms: After discontinuation of short-term and long-term treatment with pregabalin withdrawal symptoms have been observed in some patients. The following events have been mentioned: Insomia, headache, nausea, anxiety, diarrhea, flu-syndrome, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness. The patients should be informed about this at the start of the treatment.
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 dose of pregabalin.
Pregabalin should be withdrawn gradually and dosage reduced slowly over at least 1 week.
Congestive Heart Failure (CHF): Although there has been no casual relationship identified between exposure to pregabalin and CHF, there have been reports of CHF in some patients receiving pregabalin. These reactions are mostly seen in elderly cardiovascular compromised patients during pregabalin treatment for a neuropathic indication. Because there are limited data on CHF patients, pregabalin should be used with caution in these patients.
Treatment of Central Neuropathic Pain Due to Spinal Cord Injury: In the treatment of central neuropathic pain due to spinal cord injury the incidence of adverse reactions in general, CNS adverse reactions and especially somnolence was increased. This may be attributed to an additive effect due to concomitant medication (eg, antispasticity agents) needed for this condition. This could be considered when prescribing pregabalin in this condition.
Suicidal Ideation and Behavior: Suicidal ideation and behavior have been reported in patients treated with antiepileptic agents. Therefore, patients should be monitored for signs of suicidal ideation and behaviors, and appropriate treatment should be considered.
Effects on the Ability to Drive or Operate Machinery: Pregabalin may have minor or moderate influence on the ability to drive and use machines. It may cause dizziness and somnolence and therefore, may influence the ability to drive or use machines. Patients are advised not to drive, operate complex machinery or engage in other potentially hazardous activities until it is known whether Leptica affects their ability to perform these activities.
Use in pregnancy: There are no adequate data from the use of pregabalin in pregnant women. Pregabalin should not be used during pregnancy unless clearly necessary (if the benefit to the mother clearly outweighs the potential risk to the fetus).
Use in lactation: It is not known if pregabalin is excreted in the breast milk of humans. Therefore, breastfeeding is not recommended during treatment with pregabalin. Effective contraception must be used in women of childbearing potential.
Use in children: The safety and efficacy of pregabalin in children <12 years and in adolescents (12-17 years) have not been established. The use in children is not recommended.

Blood and Lymphatic System Disorders: Neutropenia.
Metabolism and Nutrition Disorders: Increased appetite, anorexia, hypoglycaemia.
Psychiatric Disorders: Euphoric mood, confusion, irritability, increased libido, disorientation, insomia, depersonalization, anorgasmia, restlessnes, depression, agitation, mood swings, depressed mood, difficulty word finding, hallucination, abnormal dreams, increased libido, panic attack, apathy, disinhibition, elevated mood.
Immune System Disorders: Hypersensitivity, allergic reaction.
Nervous System Disorders: Dizziness, somnolence, ataxia, disturbance in attention, abnormal coordination, memory impairment, tremor, dysarthria, paresthesia, sedation, lethargy, cognitive disorder, hypoesthesia, visual field, defect, nystagmus, speech disorder, myoclonus, hyporeflexia, dyskinesia, psychomotor, hyperactivity, postural dizziness, hyperesthesia, ageusia, burning sensation, intention tremor, stupor, syncope, amnesia, hypokinesia, parosmia, dysgraphia, loss of consciousness, mental impairment, headache.
Eye Disorders: Blurred vision, diplopia, visual disturbance, dry eye, eye swelling, reduced visual acuity, eye pain, asthenopia, increased lacrimation, photopsia, eye irritation, mydriasis, oscillopsia, altered visual depth perception, peripheral vision loss, strabismus, visual brightness.
Ear and Labyrinth Disorders: Vertigo, hyperacusis.
Cardiac Disorders: Tachycardia, atrioventricular block 1st-degree, sinus tachycardia and bradycardia and arrhythmia, CHF.
Vascular Disorders: Flushing, hot flushes, hypotension, hypertension, peripheral coldness.
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea, nasal dryness, nasopharyngitis, cough, nasal congestion, epistaxis, rhinitis, snoring, throat tightness.
Gastrointestinal Disorders: Dry mouth, constipation, vomiting, flatulence, abdominal distention, salivary hypersecretion, gastroesophageal reflux disease, oral hypoesthesia, ascites, dysphagia, pancreatitis, nausea, swollen tongue, diarrhea.
Skin and Subcutaneous Tissue Disorders: Sweating, papular rash, cold sweat, urticaria, Stevens-Johnson syndrome, pruritus.
Musculoskeletal and Connective Tissue Disorders: Muscle twitching, joint swelling, muscle cramp, myalgia, arthralgia, back pain, pain in limb, muscle stiffness, cervical spasm, neck pain, rhabdomyolysis.
Renal and Urinary Disorders: Dysuria, urinary incontinence, oliguria, renal failure, urinary retention.
Reproductive System and Breast Disorders: Erectile dysfunction, delayed ejaculation, sexual dysfunction, amenorrhea, breast discharge and pain, dysmenorrhea, breast hypertrophy.
General Disorders and Administration Site Conditions: Fatigue, peripheral edema, feeling drunk, edema, abnormal gait, asthenia, fall, thirst, chest tightness, exacerbated pain, anasarca, pyrexia, rigors, face edema.
Investigations: Increased weight, alanine aminotransferase, blood creatinine phosphakinase, aspartate aminotransferase, blood glucose. Decreased platelet count, blood potassium, weight, white blood cell count.
After discontinuation of short-term and long-term treatment with pregabalin, withdrawal symptoms have been observed in some patients. The following reactions have been mentioned: Insomia, headache, nausea, anxiety, diarrhea, flu-syndrome, convulsions, nervousness, depression, pain hyperhidrosis and dizziness. The patient should be informed about this at the start of the treatment.

Drugs Affecting Hepatic Microsomal Enzymes: Since pregabalin undergoes negligible metabolism in human, pharmacokinetics of Leptica are unlikely to be affected by other agents through metabolic interaction.
Protein-Bound Drugs: Because pregabalin does not bind to plasma proteins, a pharmacokinetic interaction with drugs that are highly protein bound is unlikely.
Anticonvulsants: Pharmacokinetic interaction unlikely with anticonvulsants (eg, phenytoin, carbamazepine, valproate, lamotrigine, phenobarbital, topiramate).
Antidiabetic Agents: Glyburide, insulin and metformin do not appear to affect the pharmacokinetic of pregabalin.
Oral Contraceptives, Norethisterone and/or Ethinyl Estradiol: Co-administration of pregabalin with the oral contraceptives norethisterone and/or ethinyl estradiol does not influence the steady-state pharmacokinetics of either substance.
Central Nervous System (CNS) Influencing Medications: Pregabalin may potentiate the effects of ethanol and lorazepam. There are reports of respiratory failure and coma in patients taking pregabalin and other CNS depressant medications. Pregabalin appears to be additive in the impairment of cognitive and gross motor function caused by oxycodone.

Store below 30°C.

Anticonvulsants

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

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