Prebacol

PREBACOL is a S-Red cap and S-Red Body, size "2", hard gelatin capsule containing white to off white powder. Some brownish particle of methylcobalamin observed.
Each hard gelatin capsule contains: Pregabalin Ph.Eur 75 mg, Methylcobalamin 750 mcg.

Pharmacotherapeutic group: Antiepileptics, other antiepileptics. ATC code: NO3AX16.
Pharmacology: Pharmacodynamics: Pregabalin: The active substance, pregabalin, is a gamma-aminobutyric acid analogue ((S)-3-(aminomethyl)-5-methylhexanoic acid).
Pregabalin is an oral medication that is chemically related to gabapentin (Neurontin, Gabarone). It is used for treating pain caused by neurologic diseases such as post herpetic neuralgia as well as seizures. It also is used for treating fibromyalgia. The mechanism of action of pregabalin is unknown. Pregabalin binds to calcium channels on nerves and may modify the release of neurotransmitters (chemicals that nerves use to communicate with each other). Reducing communication between nerves may contribute to pregabalin's effect on pain and seizures.
Methylcobalamin: Vitamin B12 normally plays a significant role in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production. However, many (though not all) of the effects of functions of B12 can be replaced by sufficient quantities of folic acid (vitamin B9), since B12 is used to regenerate folate in the body. Most vitamin B12 deficiency symptoms are actually folate deficiency symptoms, since they include all the effects of pernicious anemia and megaloblastosis, which are due to poor synthesis of DNA when the body does not have a proper supply of folic acid for the production of thymine. When sufficient folic acid is available, all known B12 related deficiency syndromes normalize, save those narrowly connected with the vitamin B12-dependent enzymes Methylmalonyl Coenzyme A mutase, and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase; and the buildup of their respective substrates (methylmalonic acid, MMA) and homocysteine.
Pharmacokinetics: Pregabalin: Absorption: Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within one hour. Pregabalin oral bioavailability is estimated to be greater than or equal to 90% and is independent of dose. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in C_max by approximately 25 to 30% and a delay in T_max to approximately 2.5 hours. Administration with food, however, has no clinically significant effect on the extent of absorption.
Distribution: Pregabalin has been shown to cross the blood-brain barrier in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the volume of distribution of pregabalin for an orally administered dose is approximately 0.56 U kg and is not bound to plasma proteins.
Metabolism: Pregabalin undergoes negligible metabolism in humans. Approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The major metabolite is N-methyl pregabalin.
Excretion: Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug. Renal clearance of pregabalin is 73 mL/minute.
Methylcobalamin: Methylcobalamin as adenosylcobalamin and hydroxocobalamin. These act as co-enzymes in the trans methylation of homocysteine to methionine; in the isomerisation of methylmalonyl co-enzyme to succinyl co-enzyme and with folate in several metabolic pathways respectively. Deficiency of Vitamin B12 interferes with haemopoiesis and produces megaloblastic anaemia.
Toxicology: Preclinical safety data: In conventional safety pharmacology studies in animals, pregabalin was well-tolerated at clinically relevant doses. In repeated dose toxicity studies in rats and monkeys CNS effects were observed, including hypo activity, hyperactivity and ataxia. An increased incidence of retinal atrophy commonly observed in aged albino rats was seen after long term exposure to pregabalin at exposures ≥5 times the mean human exposure at the maximum recommended clinical dose.
Pregabalin was not teratogenic in mice, rats or rabbits. Foetal toxicity in rats and rabbits occurred only at exposures sufficiently above human exposure. In prenatal/postnatal toxicity studies, pregabalin induced offspring developmental toxicity in rats at exposures >2 times the maximum recommended human exposure.
Adverse effects on fertility in male and female rats were only observed at exposures sufficiently in excess of therapeutic exposure. Adverse effects on male reproductive organs and sperm parameters were reversible and occurred only at exposures sufficiently in excess of therapeutic exposure or were associated with spontaneous degenerative processes in male reproductive organs in the rat. Therefore the effects were considered of little or no clinical relevance. Pregabalin is not genotoxic based on results of a battery of in vitro and in vivo tests.
Two-year carcinogenicity studies with pregabalin were conducted in rats and mice. No tumours were observed in rats at exposures up to 24 times the mean human exposure at the maximum recommended clinical dose of 600 mg/day. In mice, no increased incidence of tumour was found at exposures similar to the mean human exposure, but an increased incidence of haemangiosarcoma was observed at higher exposures. The non-genotoxic mechanism of pregabalin-induced tumour formation in mice involves platelet changes and associated endothelial cell proliferation. These platelet changes were not present in rats or in humans based on short term and limited long term clinical data. There is no evidence to suggest an associated risk to humans.
In juvenile rats, the types of toxicity do not differ qualitatively from those observed in adult rats. However, juvenile rats are more sensitive. At therapeutic exposures, there was evidence of CNS clinical signs of hyperactivity and bruxism and some changes in growth (transient body weight gain suppression). Effects on the oestrus cycle were observed at 5-fold the human therapeutic exposure. Reduced acoustic startle response was observed in juvenile rats 1-2 weeks after exposure at >2 times the human therapeutic exposure. Nine weeks after exposure, this effect was no longer observable.

Possesses anxiolytic, analgesic and anticonvulsant activity.
Possesses high bioavailability (90% vs 33-66%) compared to gabapentin.
Highly effective in relieving the neuropathic pain.
Improves mood and reduces sleep disturbance.
Acts as neuroprotective, promotes myelination in neurons.
Relieves burning sensation, numbness, and loss of sensation & muscle cramps in diabetic neuropathy.
Peripheral neuropathy.
Diabetic neuropathy.
Drug-induced neuropathy.

For adults one capsule two or three times daily or as directed by physician. Pregabalin and Methylcobalamin Capsule (PREBACOL) should be taken before food intake.

Pregabalin: In the post-marketing experience, the most commonly reported adverse reactions observed when pregabalin was taken in overdose included somnolence, confusional state, agitation, and restlessness. In rare occasions, cases of coma have been reported.
Treatment of pregabalin overdose should include general supportive measures and may include haemodialysis if necessary.
Methylcobalamin: No any serious effect due to overdose.

Hypersensitivity.
Pregnancy, lactation.
Driving or working with machines.
Doing other dangerous activities.

May cause peripheral edema.
Regular vision check is recommended.
May decrease platelet count and prolong RR interval.
Discontinue treatment if patients develop severe angioedema.
Withdraw treatment gradually over at least 1 week.
Use in Children: Safety and effectiveness in paediatric patients have not been established.

Pregnancy: Pregnancy Category C: Increased incidences of fetal structural abnormalities and other manifestations of development toxicity, including lethality, growth retardation and nervous and reproductive system functional impairment, were observed in the offspring of rats and rabbits given pregabalin during pregnancy at doses that produced plasma pregabalin exposures (AUC) ≥5 times human exposure at the maximum recommended dose of 600 mg/day. There are no adequate and well-controlled studies in pregnant women. Pregabalin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: 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.

Dizziness, drowsiness, visual disturbance (including blurred vision, diplopia), ataxia, dysarthria, tremor, lethargy, memory impairment, euphoria, weight gain, constipation, dry mouth, peripheral edema, depression, confusion, agitation, hallucinations, myoclonus, hypoaesthesia, hyperaesthesia, tachycardia, excessive salivation, sweating, flushing, rash, muscle cramp, myalgia, arthralgia, urinary incontinence, dysuria, thrombocytopenia, neutropenia, first-degree heart block, hypotension, hypertension, pancreatitis, dysphagia, oliguria, rhabdomyolysis.

Concurrent use with oxycodone, lorazepam and ethanol may increase the CNS effects.

Special Precautions for Disposal and Other Handling: No special requirements.

Store at temperature not exceeding 30°C. Protect from light.
Shelf Life: 36 months.

Drugs for Neuropathic Pain

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

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