Mebaal Plus-150

Mebaal Plus-150

Manufacturer:

Inventia

Distributor:

Maxxcare

Marketer:

Mega Lifesciences
Full Prescribing Info
Contents
Methylcobalamin, pregabalin.
Description
Each uncoated bilayered tablets contains: Methylcobalamin 1500 mcg, Pregabalin (in sustained release form) 150 mg.
MEBAAL Plus-150 is a brand of Methylcobalamin with sustained release Pregabalin.
Methylcobalamin is one of the two coenzyme forms of vitamin B12 (cyanocobalamin). Vitamin B12 plays an important role in the maturation of red blood cells, methylation reactions, and immune system regulation.
The chemical name of Methylcobalamin is Coα-[α-(5,6-dimethylbenz-1H-imidazolyl)]-Coβmethylcobamide]. Its empirical formula is C63H91CoN13O14P and molecular weight is 1344.40.
Pregabalin is a 3-substituted analogue of gamma-amino butyric acid (GABA) having a similar pharmacological profile to that of gabapentin. The chemical name of Pregabalin is (S)-3-(aminomethyl)-5-methylhexanoic acid. Its empirical formula is C8H17NO2 and molecular weight is 159.23.
Excipients/Inactive Ingredients: Cetyl alcohol BP, Polysorbate 80 BP, Mannitol BP, Microcrystalline cellulose BP, Povidone BP, Purified talc BP, Magnesium stearate BP, Isopropyl alcohol BP, Hypromellose USP, Macrogol BP, Sodium bicarbonate BP, Purified water BP.
Action
Pharmacology: Pharmacodynamics: Methylcobalamin: Synthesis of the myelin coating of peripheral nerves requires adequate availability of vitamin B12.
Myelin is a lipoprotein and Methylcobalamin participates in the synthesis of phospholipid and the protein components.
Lipid synthesis: Methylcobalamin supplies necessary methyl group for phospholipid (also referred to as lecithin, the main constituent of medullary sheath lipids) manufacturing.
Protein synthesis: Methylcobalamin also upregulates gene transcription resulting in protein synthesis stimulation.
Even in Wallerian degeneration, wherein the nerve is crushed, Methylcobalamin has ability to regenerate it and improve conduction.
MEBAAL Plus provides vitamin B12 in its active form as Methylcobalamin (Mecobalamin).
Supplementing the active form of vitamin B12 namely Methylcobalamin is always advantageous since it ensures adequate direct availability of vitamin B12 without depending on the body for conversion from cyanocobalamin (a form of vitamin B12 usually taken) to Methylcobalamin. Both vitamin B12 and folic acid are required for synthesis of deoxyribonucleic acid (DNA). Folic acid exists as methyl folate in body. A vitamin B12 - containing enzyme removes a methyl group from the latter thereby converting methyl folate to tetrahydrofolicacid (THFA). It is THFA that is involved in DNA synthesis.
Pregabalin: Neuropathic pain generally does not respond to treatment with opioid or nonsteroidal anti-inflammatory drugs NSAIDs. Data from clinical studies have demonstrated that Pregabalin shares similar analgesic effectiveness as gabapentin for neuropathy pain. Besides, Pregabalin is also effective for epilepsy and fibromyalgia.
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, binding to the alpha2-delta subunit may be involved in MEBAAL Plus's antinociceptive and antiseizure effects. Pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function.
While Pregabalin is a structural derivative of the inhibitory neurotransmitter gammaaminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses nor does it alter brain GABA concentration or have acute effects on GABA uptake or degradation. However, Pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity, it is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin or noradrenaline reuptake.
Pharmacokinetics: Methylcobalamin: Methylcobalamin and cyanocobalamin are similarly absorbed from the gastrointestinal (GI) tract. The cobalamine are bound to specialized transport proteins intrinsic factor (of stomach), which facilitates their entry into the cells lining the intestinal mucosa. Entry in the physiological conditions occurs only via the ileum. Inside the body, Methylcobalamin is transported into all other cells only when bound to another transport protein, transcobalamin II.
The Cmax of B12 is reached in 3 hours. Following single dose intake of 1500 mcg, the Cmax obtained is 972 pg/ml. In the liver significantly more cobalamin accumulates following methylcobalamin intake than cyanocobalamin. 40-80% of total B12 is excreted in urine in 24 hours. Human Methylcobalamin urinary excretion is about one-third that of a similar dose of cyanocobalamin, indicating substantial greater tissue retention.
Pregabalin: Pregabalin is well absorbed after oral administration of MEBAAL Plus, and the rate of absorption is decreased when given with food, resulting in a decrease in maximum blood concentrations (Cmax) of approximately 25% to 30% and an increase in times taken for Cmax (Tmax) to approximately 3 hours.
However, administration of Pregabalin with food has no clinically relevant effect on the total absorption of Pregabalin. Therefore, MEBAAL Plus can be taken with or without food.
The oral bioavailability of Pregabalin is 90% and is independent of dose. Following repeated administration, steady state is achieved within 24 to 48 hours.
Pregabalin does not bind to plasma proteins. The apparent volume of distribution of Pregabalin following oral administration is approximately 0.5 L/kg. Pregabalin is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. In addition to crossing the blood-brain barrier, Pregabalin also crosses the placenta and is present in the milk during lactation.
Pregabalin undergoes negligible metabolism in humans. Following an oral dose of MEBAAL Plus, approximately 90% of it is recovered in the urine as unchanged Pregabalin. The N-methylated derivative, the major metabolite of Pregabalin found in urine, accounts 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 of 6.3 hours in subjects with normal renal function. Mean renal clearance is estimated to be 67.0 to 80.9 ml/min in young healthy subjects. Because Pregabalin is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to creatinine clearance.
Indications/Uses
MEBAAL Plus-150 is indicated for painful neuropathies such as: Diabetic neuropathy; Post-herpetic neuralgia; Trigeminal neuralgia; Following nerve entrapment as in prolapsed intervertebral disc; Complex regional pain syndrome; Infective neuropathies; HIV sensory neuropathy; Alcoholic neuropathy; Nutritional neuropathies; Phantom limb pain.
Dosage/Direction for Use
ADULTS: The usual dose is one MEBAAL Plus-150 tablet once daily which can be increased as required up to 600 mg Pregabalin/day. MEBAAL Plus-150 tablet once daily can be taken with/without food. Increase dose as necessary to 1 MEBAAL Plus-150 tablet b.i.d with/without food. Dosage above 300 mg/day must be reserved only for those having on-going pain, and tolerating 300 mg Pregabalin per day. Whilst discontinuing MEBAAL Plus-150, the dose of Pregabalin must be gradually reduced over 1 week.
Dosage in Renal Dysfunction: Creatinine clearance 30-60 ml/min: 300 mg Pregabalin per day maximum dose.
Creatinine clearance 15-30 ml/min: 150 mg Pregabalin per day maximum dose.
Creatinine clearance <15 ml/min: 75 mg Pregabalin per day maximum dose.
Mode of Administration: Oral.
Overdosage
Methylcobalamin: Toxicity due to overdosage with Methylcobalamin is not known.
Pregabalin: 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. In clinical studies, some patients took as much as 2400 mg/day. 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 patient's clinical state or in patients with significant renal impairment. Standard hemodialysis procedures result in significant clearance of Pregabalin (approximately 50% in 4 hours).
Contraindications
MEBAAL Plus is not advocated to those hypersensitive to the drug or to any of its ingredients.
Warnings
Pregabalin may cause dizziness, somnolence and other symptoms and signs of central nervous system depression. Accordingly, the advice is neither to drive a car nor to operate other complex machinery until sufficient experience has been gained on MEBAAL Plus to gauge whether or not it affects the mental and/or motor performance adversely. If vision disturbances occur during Pregabalin therapy, medical advice must be sought. Also unexplained muscle pain, tenderness, or weakness, especially accompanied by malaise or fever requires prompt medical attention.
MEBAAL Plus must be advocated with caution in heart failure and diabetic patients in view of possibility of edema and weight gain induced by Pregabalin. Diabetic patients taking Pregabalin may develop skin ulcerations. MEBAAL Plus must be advocated with due precaution in renal dysfunction.
MEBAAL Plus must be advocated with caution along with thiazolidinediones in view of weight gain and fluid retention possibility with both these agents. It is not to be taken along with alcohol, or be combined with other central nervous depressants.
Antiepileptic drugs such as MEBAAL Plus should not be abruptly discontinued because of the possibility of increasing seizure frequency; rapid discontinuation may result in insomnia, nausea, headache, or diarrhea. MEBAAL Plus is not intended solely for treatment of anemias or providing vitamin A, for those nutritionally deficient in it.
MEBAAL Plus, like any other anti-epileptic drug must not be discontinued abruptly due to the possibility of increasing seizure frequency; rapid discontinuation may also, result in insomnia, nausea, headache, or diarrhea. If MEBAAL Plus is to be stopped, it must be done gradually over 1 week. It has been demonstrated, but not conclusively, that intake of Pregabalin could cause new, or worsening of preexisting tremors.
Since Pregabalin can cause dizziness, somnolence and other manifestations of central nervous system depression, patients should be advised neither to drive nor to operate complex machinery until they have gained sufficient experience on MEBAAL Plus to gauge whether or not it affects their mental and/or motor performance adversely.
If vision disturbances occur during Pregabalin therapy, medical advice must be sought. Also unexplained muscle pain, tenderness, or weakness, especially accompanied by malaise or fever requires prompt medical attention.
MEBAAL Plus must be advocated with caution along with thiazolidinediones in view of weight gain and fluid retention possibility with both these agents. It is not to be taken along with alcohol, or be combined with other central nervous depressants.
Special Precautions
MEBAAL Plus must be advocated with caution in heart failure and diabetic patients in view of possibility of edema and weight gain induced by Pregabalin. Diabetic patients taking Pregabalin may develop skin ulcerations. MEBAAL Plus must be advocated with due precaution in renal dysfunction. Those with early Leber's disease (hereditary optic nerve atrophy) when treated with vitamin B12 can suffer from severe and swift optic atrophy and consequently MEBAAL Plus must be advocated with due precaution.
Effects on ability to drive and use machines: Driving or operating complex machinery not recommended.
Use In Pregnancy & Lactation
MEBAAL Plus should be used during pregnancy (Category: Pregabalin, C; Methylcobalamin, B) and lactation only if the potential benefit justifies the probable risks involved. The safety and efficacy of Pregabalin in children have not been established.
Adverse Reactions
Methylcobalamin: Methylcobalamin is relatively safe and devoid of side effects. However, it could infrequently cause the following reactions.
Cardiovascular: pulmonary edema and congestive heart failure early in treatment; peripheral vascular thrombosis.
Hematological: Polycythemia Vera.
Gastrointestinal: mild transient diarrhea.
Dermatological: itching; transitory exanthema.
Miscellaneous: feeling of swelling of entire body.
Pregabalin: The common adverse effects of pregabalin given alone, or in combination with other anti-epileptic agents are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and "thinking abnormal" (primarily difficulty with concentration/attention). Asthenia, ataxia, abnormal gait, paresthesias, diplopia, blurred vision, visual field defect, nystagmus, nausea, tremor, vertigo, headache, nervousness, confusion and edema are other significant side effects of pregabalin.
Effects are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; Infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.
Body as a whole: Frequent: Abdominal pain, Allergic reaction, Fever, Flu syndrome, accidental injury; Infrequent: Abscess, Cellulitis, Chills, Malaise, Neck rigidity, Overdose, Pelvic pain, Chest pain, Photosensitivity reaction, Suicide attempt; Rare: Anaphylactoid reaction, Ascites, Granuloma, Hangover effect, Intentional injury, Retroperitoneal Fibrosis, Shock, Suicide.
Cardiovascular system: Infrequent: Deep thrombophlebitis, Heart failure, Hypotension, Postural hypotension, Retinal vascular disorder, Syncope; Rare: ST depressed, Ventricular Fibrillation.
Digestive System: Frequent: Gastroenteritis, Nausea, Diarrhea, Flatulence, Dry mouth, Increased appetite, Constipation; Infrequent: Cholecystitis, Cholelithiasis, Colitis, Dysphagia, Esophagitis, Gastritis, Gastrointestinal hemorrhage, Melena, Mouth ulceration, Pancreatitis, Rectal hemorrhage, Tongue edema; Rare: Aphthous stomatitis, Esophageal ulcer.
Hemic and Lymphatic System: Frequent: Ecchymosis; Infrequent: Anemia, Eosinophilia, Hypochromic anemia, Leukocytosis, Leukopenia, Lymphadenopathy, Thrombocytopenia; Rare: Myelofibrosis, Polycythemia, Prothrombin decreased, Purpura, Thrombocytopenia.
Metabolic and Nutritional Disorders: Frequent: Weight gain, Peripheral edema; Rare: Glucose Tolerance Decreased, Hypoglycemia, Urate crystalluria.
Musculoskeletal System: Frequent: Arthralgia, Leg cramps, Myalgia, Myasthenia; Infrequent: Arthrosis; Rare: Generalised Spasm.
Nervous System: Frequent: Headache, Nervousness, Dizziness, Vertigo, Somnolence, Ataxia, Tremor, Thinking abnormal, Amnesia, Speech disorder, Incoordination, Abnormal gait, Twitching, Confusion, Anxiety, Depersonalization, Hypertonia, Hypesthesia, Libido decreased, Nystagmus, Paresthesia, Stupor, Twitching, Euphoria; Infrequent: Abnormal dreams, Agitation, Apathy, Aphasia, Circumoral paresthesia, Dysarthria, Hallucinations, Hostility, Hyperalgesia, Hyperesthesia, Hyperkinesia, Hypokinesia, Hypotonia, Libido increased, Myoclonus, Neuralgia; Rare: Addiction, Cerebellar syndrome, Cogwheel rigidity, Coma, Delirium, Delusions, Dysautonomia, Dyskinesia, Dystonia, Encephalopathy, Extrapyramidal syndrome, Guillain Barre syndrome, Hypoalgesia, Intracranial hypertension, Manic reaction, Paranoid reaction, Peripheral neuritis, Psychotic depression, Schizophrenic reaction, Torticollis, Trismus.
Respiratory System: Frequent: Bronchitis, Dyspnea; Rare: Apnea, Atelectasis, Bronchiolitis, Hiccup, Laryngismus, Lung edema, Lung fibrosis, Yawn.
Skin and Appendages: Frequent: Pruritus, Face swelling; Infrequent: Alopecia, Dry skin, Eczema, Hirsutism, Skin ulcer, Urticaria, Vesiculobullous rash; Rare: Angioedema, Exfoliative dermatitis, Lichenoid dermatitis, Melanosis, Petechial rash, Purpuric rash, Pustular rash, Skin atrophy, Skin necrosis, Skin nodule, Stevens Johnson syndrome, Subcutaneous nodule.
Special senses: Frequent: Conjunctivitis, Diplopia, Blurred vision, Abnormal vision, Otitis media, Tinnitus; Infrequent: Abnormality of accommodation, Blepharitis, Dry eyes, Eye hemorrhage, Hyperacusis, Photophobia, Retinal edema, Taste loss, Taste perversion; Rare: Anisocoria, Blindness, Corneal ulcer, Exophthalmos, Extraocular, Palsy, Iritis, Keratitis, Keratoconjunctivitis, Miosis, Mydriasis, Night blindness, Ophthalmoplegia, Optic atrophy, Papilledema, Parosmia, Ptosis, Uveitis.
Urogenital System: Frequent: Anorgasmia, Impotence, Urinary frequency, Urinary incontinence; Infrequent: Abnormal ejaculation, Albuminuria, Amenorrhea, Dysmenorrhea, Dysuria, Hematuria, Kidney calculus, Leukorrhea, Metrorrhagia, Nephritis, Oliguria, Urinary retention; Rare: Acute kidney failure, Balanitis, Bladder Neoplasm, Cervicitis, Dyspareunia, Epididymitis, Female lactation, Glomerulitis.
Drug Interactions
Gabapentin may slightly decrease the rate of absorption of Pregabalin when administered together.
Storage
Store below 25°C in a dry place.
Protect from light and moisture.
Shelf life: 24 months.
ATC Classification
N03AX16 - pregabalin ; Belongs to the class of other antiepileptics.
Presentation/Packing
Tab (circular, biconvex, bevelled edge, bilayered, uncoated with one layer i.e. Pregabalin layer white in color and other layer i.e. Methylcobalamin layer mottled pink in color, plain on both sides) 3 x 10's.
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