Emaxgalin

Uses

Etoricoxib is used for relief of pain and inflammation in-

• Osteoarthritis
• Rheumatoid arthritis
• Other chronic musculoskeletal disorders
• Acute gout
• Dysmenorrhoea
• Following dental surgery

Pregabalin is used for the management of neuropathic pain associated with diabetic peripheral neuropathy and management of post-herpetic neuralgia. It is also used for the adjunctive therapy for adult patients with partial onset seizures. It can be used for the management of fibromyalgia and neuropathic pain associated with spinal cord injury.

Emaxgalin is also used to associated treatment for these conditions: Ankylosing Spondylitis (AS), Gouty Arthritis, Osteoarthritis (OA), Rheumatoid Arthritis, Moderate PainDiabetic Peripheral Neuropathic Pain (DPN), Epilepsies, Fibromyalgia, Generalized Anxiety Disorder (GAD), Neuropathic Pain, Partial-Onset Seizures, Peripheral Neuropathic Pain, Peripheral neuropathy, Postherpetic Neuralgia

How Emaxgalin works

Like any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid.

Although the mechanism of action has not been fully elucidated, studies involving structurally related drugs suggest that presynaptic binding of pregabalin to voltage-gated calcium channels is key to the antiseizure and antinociceptive effects observed in animal models.

By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action.

Although pregabalin is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors.

Dosage

Emaxgalin dosage

The recommended dose for adult and patient over 16 years:

• Acute pain: 120 mg once daily. Etoricoxib 120 mg should be used only for acute symptomatic period, limited to a maximum of 8 days treatment.
• Chronic musculoskeletal pain: 60 mg once daily.
• Osteoarthritis: 30 mg once daily, increased if necessary to 60 mg once daily.
• Rheumatoid arthritis and ankylosing spondylitis: 90 mg once daily.
• Acute gout: 120 mg once daily for max. 8 days. Max. 60 mg daily in mild hepatic impairment; max. 60 mg on alternate days or 30 mg once daily in moderate hepatic impairment.

Neuropathic pain associated with diabetic peripheral neuropathy: 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.

Post-herpetic neuralgia: The recommended dose of Pregabalin is 75 to 150 mg two times a day, or 50 to 100 mg three times a day (150 to 300 mg/day) in patients with creatinine clearance of at least 60 mL/min. Dosing should begin at 75 mg two times a day, or 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.

Adjunctive therapy for adult patients with partial onset seizures: 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 doseshould be divided and given either two or three times daily. 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.

Management of Fibromyalgia: The recommended dose of Pregabalin for fibromyalgia is 300 to 450 mg/day. Dosing should begin at 75 mg two times a day (150 mg/day) and may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day).

Neuropathic pain associated with spinal cord injury: The recommended dose range is 150 to 600 mg/day. The recommended starting dose is 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability.

.Patients who do not experience sufficient pain relief after treatment with 300 mg/day and who tolerate pregabalin may be treated with up to 300 mg two times a day. Neurolin® capsules can be taken without regards to meals.

Side Effects

Dry mouth, taste disturbance, mouth ulcer, flatulence, constipation, appetite and weight changes, chest pain , fatigue, paraesthesia, influenza like syndrome, myalgia etc. may occur.

The most common side effects include dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and abnormal thinking.

Toxicity

This reduced activity is the cause of reduced gastrointestinal toxicity, as demonstrated in several large clinical trials performed with different COXIB (see below links on NEJM and The Lancet). Some clinical trials and meta-analysis showed that treatment with COXIB lead to increased incidence of cardiovascular adverse events compared to placebo

In a systematic review that included 38 randomized controlled trials, there were 20 identified adverse effects that were significantly associated with pregabalin, most of which involve the central nervous system and cognition. The identified adverse effects include vertigo, dizziness, balance disorder, incoordination, ataxia, blurred vision, diplopia, amblyopia, somnolence, confusional state, tremor, disturbance in attention, abnormal thinking, asthenia, fatigue, euphoria, edema, peripheral edema, dry mouth, and constipation .

The most common symptoms of pregabalin toxicity (dose range includes 800 mg/day and single doses up to 11,500 mg) include somnolence, confusion, restlessness, agitation, depression, affective disorder and seizures.

Since there is no antidote for pregabalin overdose, patients should receive general supportive care. If appropriate, gastric lavage or emesis may help eliminate unabsorbed pregabalin (healthcare providers should take standard precautions to maintain the airway).

Pregabalin pharmacokinetic properties suggest that extra-corporeal elimination methods including haemodialysis, may be useful in situations of severe toxicity. However, there are cases where patients have presented with very high serum levels of pregabalin and have been successfully managed with supportive care alone.

Precaution

A patient with decreased liver & kidney function, dehydration, hypertension, heart failure, GI perforation & patients over 65 years of age. Use in Pregnancy and Lactation As with other drugs known to inhibit prostaglandin synthesis, use of it should be avoided in late pregnancy because it may cause premature closure of the ductus arteriosus. It should be used during the first two trimesters of pregnancy only if the potential benefit justifies the potential risk to the foetus. It is not known whether this drug is excreted in human milk.

Discontinuation of Pregabalin without tapering may produce insomnia, nausea, headache and diarrhea. So it should be tapered gradually over a minimum of 1 week rather than discontinued abruptly. Creatinine kinase may be elevated if treated with Pregabalin. It should be discontinued rapidly if myopathy is diagnosed or suspected or if creatinine kinase is elevated markedly.

Interaction

Oral anticoagulants, diuretics and ACE inhibitors, Acetylsalicylic acid, Cyclosporin and Tacrolimus, Lithium, Methotrexate, oral contraceptives, Prednisone/Prednisolone, Digoxin, drugs metabolized by sulfotransferases (Ethinyl Estradiol), drugs metabolized by CYP isoenzymes, Ketoconazole, Rifampicin, and Antacids have interaction with Etoricoxib.

Volume of Distribution

After oral administration of pregabalin, the reported apparent volume of distribution is roughly 0.5 L/kg.

Although pregabalin is not very lipophilic, it is able to cross the blood brain barrier(BBB). System L transporters facilitate the transport of large amino acids across the BBB and it has been confirmed that pregabalin is a substrate. This information suggests that system L transporters are responsible for pregabalin uptake into the BBB.

In rat models, pregabalin has been shown to cross the placenta.

Elimination Route

Bioavailability is 100% following oral administration.

After oral dosing administered in the fasted state, pregabalin absorption is rapid, and extensive. Pregabalin oral bioavailability is reported to be ≥90% regardless of the dose. Cmax is attained within 1.5 hours after single or multiple doses, and steady state is attained within 24-48 hours with repeated administration. Both Cmax and AUC appear to be dose proportional.

Food decreases the rate of pregabalin absorption and as a result, lowers the Cmax by an estimated 25-30% and increases the Tmax to approximately 3 hours. However, the effect of food does not appear to impact the total absorption of pregabalin in a way that is clinically relevant. As a result, pregabalin can be administered with or without food.

Half Life

22 hours

The elimination half life of pregabalin is 6.3 hours.

Clearance

In young healthy subjects the mean renal clearance is estimated to be 67.0 to 80.9 mL mL/min. Given pregabalin's lack of plasma protein binding, this clearance rate suggests that renal tubular reabsorption is involved.

Elimination Route

Pregabalin is almost exclusively eliminated in the urine.

Further, based on preclinical studies, pregabalin does not appear to undergo racemization to the R enantiomer in the body.

Pregnancy & Breastfeeding use

As with other drugs known to inhibit prostaglandin synthesis, use of it should be avoided in late pregnancy because it may cause premature closure of the ductus arteriosus. It should be used during the first two trimesters of pregnancy only ifthe potential benefit justifies the potential risk to the foetus. It is not known whether this drug is excreted in human milk.

Pregnancy category C. So it should only used if potential benefit justifies the potential risks to the fetus.

Nursing mother: It is not known if pregabalin is excreted in human milk; it is, however, present in the milk of rats. So it should be used in nursing mother only if there is a clear benefit over the risk.

Contraindication

It is contraindicated in patients with hypersensitivity to Etoricoxib or any component of this product, congestive heart failure, patients with inflammatory bowel disease, severe hepatic dysfunction.

Pregabalin is contraindicated in patients with known hypersensitivity to Pregabalin or any of its components.

Special Warning

Use in children & adolescents: The safety and effectiveness of Pregabalin have not been established in patients below the age of 18 years.

Use in elderly (Over 65 years of age): No dosage adjustment is necessary in elderly patients. Overdose: In overdoses up to 15 g, no unexpected adverse effects were reported.

Paediatric use: The safety and efficacy of pregabalin in paediatric patients have not been established.

Acute Overdose

Symptoms: GI and cardiorenal events.

Management: Symptomatic and supportive treatment. Remove unabsorbed material from the GI tract.

Storage Condition

Store at a cool & dry place protected from light & moisture. Keep out of reach of children.

Store at a cool & dry place, protected from light and moisture. Keep out of reach of the children.

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