Biopentin Tablet Composition, Use, Side Effect, Dose

Biopentin tablet is a drug designed for pain. It is manufactured in India by pulse pharmaceuticals Pvt., LTD and marketed in Nigeria by Biogen pharmaceuticals LTD. It comes in a tablet of 10 in a sachet.

Biopentin tablet

Composition Of Biopentin

Each film coated tablet contains:

Gabapentin USP 300 mg

Methylcobalamin 500mcg

Excipients: qs

Color: Sunset Yellow and Titanium dioxide BP

Description

Neuropathic pain of varied etiology is caused by a primary lesion or dysfunction in the nervous system, where pain is a primary manifestation. Studies have revealed that a disorder of the myelin in both the CNS and the PNS is a feature in the majority of the neuropathies. There is demyelination of the spinal cord, brain, optic and peripheral nerves leading to cell degeneration, loss of nerve function and finally damaged nerve fibres.

Gabapentin prevents pain-related responses in neuropathic pain. Methylcobalamin improves nerve function by contributing to nerve myelination, stimulating protein synthesis for neural regeneration and repair. In peripheral neuropathies, regenerate neurons and myelin sheath that protect nerve axons and peripheral nerves thereby facilitating normal cell growth.

Postherpetic neuralgia (PHN) is most commonly defined as pain in the area affected by herpes zoster at least 3 months after crusting of the herpes zoster rash. Once established, PHN may persist for many years.

Gabapentin is described as 1 (aminomethyl cyclohexane acetic acid) with a molecular formula of C9H17NO2 and a molecular weight of 171.24.

Methylcobalamin is one of the two coenzyme forms of vitamin B12 (the other being adenosylcobalamin). It is a cofactor in the enzyme methionine synthase which functions to transfer methyl groups of the regeneration of methionine from homocysteine.

Mode Of Action And Clinical Pharmacology Of Biopentin

Gabapentin

Action is potentially via binding to the alpha 2 delta subunits of voltage gated calcium channels and inhibition of glutamate release presynaptically and post-synaptically in the CNS. It also stabilizes the nerve membrane by inhibiting calcium ion channels, therefore minimizing abnormal synthesis / firing of impulses.

Methylcobalamin

Methylcobalamin is the neurologically active form of vitamin B12, which increases myelin sheath formation and regenerates neurons and prevents progressive nerve damage.

Pharmacokinetics And Metabolism Of Biopentin

Gabapentin

Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours. Absolute bioavailability of 300 mg gabapentin tablets is approximately 55%. Food has no effect on gabapentin pharmacokinetics. Gabapentin elimination parameters are independent of dose.

However, the extent of gabapentin absorption decreases with increasing dose. Following doses of 300 and 600 mg, absolute bioavailability is 57% and 42% respectively. In normal volunteers the elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.

Gabapentin is not bound to plasma proteins and has an apparent volume of distribution of 57.7 liters. In patients with epilepsy, gabapentin concentrations in CSF ranged from 7-35% of corresponding steady state through plasma concentrations. Gabapentin is eliminated solely by renal excretion.

Gabapentin does not include hepatic mixed-function oxidase enzymes responsible for drug metabolism. In elderly patients, age-related alterations in renal function decrease gabapentin plasma clearance and increase gabapentin elimination half-life. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance. Gabapentin is removed from plasma by haemodialysis.

Methylcobalamin

In a four-month, double-blind, placebo-controlled trial of type 1 and 2 diabetics with neuropathy, 21 subjects were given oral methylcobalamin at a dose of 500 mcg three times daily, while 22 subjects received placebo. Significant improvements were reported for somatic and autonomic symptoms in the treatment group compared to placebo.

Diabetic Neuropathy

Oral administration of methylcobalamin (500 mg three times daily for four months) resulted in subjective improvement in burning sensations, numbness, loss of sensation, and muscle cramps. An improvement in reflexes, vibration sense, lower motor neuron weakness, and sensitivity to pain was also observed.

Single-dose administration

When methylcobalamin was administered orally to healthy adult male volunteers at a single dose of 120 mcg and 1500 mpg, the peak serum total vitamin B12 (abbreviated to 812) concentration was reached 3 hr for both doses, and this was dose-dependent.

Repeated-dose administration

Methylcobalamin was administered orally to healthy adult male volunteers at a dose of 1500 mg daily for consecutive 12 weeks and changes in the serum total vitamin B12 concentration were determined until 4 weeks after the last administration. The serum concentration increased for the first 4 weeks after administration, reaching about twice as high as the initial value.

Thereafter, there was a gradual increase which reached a peak of about 2.6 times the initial value at the 12th week of dosing. The serum concentration declined after the last administration (12 weeks), but was still about 1.8 times the initial value 4 weeks after the last administration.

Indications And Use Of Biopentin

Treatment of diabetic and non diabetic neuropathic pain and postherpetic neuralgia.

Contra-indications

Hypersensitivity to cobalamin products or gabapentin or any component of the preparation. Tobacco amblyopia should not be administered before pernicious anemia or folate deficiency has been ruled out. Gabapentin is contraindicated in breast-feeding, pregnancy, carcinogenicity, when driving and with alcohol. For Methylcobalamin there are no independent and relative contraindications.

Drug Interaction

Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly co administered antiepileptic drugs.

Hydrocodone: Co administration of Gabapentin decreases hydrocodone Cmax and AUC values in a dose-dependent manner relative to the administration of hydrocodone alone; hydrocodone increases Gabapentin AUC values by 14%.

Morphine: Patients who require concomitant treatment with morphine may experience increases in Gabapentin concentrations. Patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of Gabapentin or morphine should be reduced appropriately.

Cimetidine: Cimetidine appeared to alter the renal excretion of both Gabapentin and creatinine, an endogenous marker of renal function. The effect of Gabapentin on cimetidine was not evaluated.

Oral contraceptive: The Cmax of norethindrone was reported to be 13% higher when it was co administered with Gabapentin. This interaction is not expected to be of clinical importance.

Antacid: It is recommended that Gabapentin be taken at least two hours following administration of an antacid.

Effect of probenecid: Probenecid is a blocker of renal tubular secretion. Gabapentin pharmacokinetic parameters without and with probenecid were comparable. This indicates that Gabapentin does not undergo renal tubular secretion by the pathway that is blocked by probenecid.

Methylcobalamin

Tetracycline: Vitamin B12 should not be taken at the same time as the antibiotic Tetracycline because it Interferes with the absorption and effectiveness of this medication. Vitamin B12 either alone or in combination with other B vitamins should be taken at different times of the day from tetracycline.

Chemotherapy Medications: Blood levels of Vitamin B12 may be reduced when taking chemotherapy medications (particularly methotrexate) for cancer.

Absorption of cobalamin is impaired by alcohol, vitamin B6 (pyridoxine) deficiency, cholestyramine, para-aminosalicylic acid colchicines, neomycin, the oral biguanides, metformin, histamine H2 receptor antagonists (cimetidine, ranitidine, etc.), phenformin and possibly potassium chloride. A number of anticonvulsants-phenobarbitone, primidone, phenytoin, and ethyl phenacemide can alter the metabolism of cobalamin in the cerebrospinal fluid and lead to neuropsychiatric disturbances.

Several substituted amide, lactone and lactum analogues of cyanocobalamin compete with binding sites on intrinsic factors and lead to depressed absorption of the vitamins. Nitrous oxide also interferes with cobalamin metabolism.

Warnings And Precautions

Gabapentin may cause dizziness, somnolence and other symptoms and signs of CNS depression. Accordingly, patients who are on the drug should be advised neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on the drug to gauge the effects of the drug on their mental and/or motor performance adversely.

Patients who require concomitant treatment with morphine may experience increases in Gabapentin concentrations. Patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of Gabapentin or morphine should be reduced appropriately.

Drug withdrawal: Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency in patients with epilepsy.

Tumorigenic Potential: Clinical experience during Gabapentin's premarketing development provides no direct means to assess its potential for inducing tumors in humans. It is reported that in clinical studies in adjunctive therapy in epilepsy comprising 2085 patients-years of exposure in patients > 12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lungs, 1 adrenal, 1 non-Hodgkin's lymphoma, 1 endometrial carcinoma in situ), and pre existing tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of Gabapentin. Without knowledge of the background incidence and recurrence in a similar population not treated with Gabapentin, it is impossible to know whether the incidence seen in this cohort is or is not affected by treatment.

Carcinogenesis, mutagenesis, and impairment of fertility: The carcinogenic risk of Gabapentin in humans is unclear. Gabapentin was not found to have mutagenic or genotoxic potential and it also had no adverse effect on fertility or reproduction in animal studies.

Pregnancy: This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in nursing mothers: Gabapentin should be used in women who are nursing only if the benefits clearly outweigh the risks.

Pediatric use: Safety and effectiveness of Gabapentin in the management of postherpetic neuralgia have not been established.

Methylcobalamin: The prolonged use of larger doses of methylcobalamin is not recommended for patients whose occupation requires the handling of mercury or mercury compounds.

Use cautiously in patients with hypertension, cardiovascular and lung diseases. Cardiac arrhythmias secondary to hypokalemia during initial therapy have been reported.

Vitamin B12 should be given prophylactically only when there is a reasonable indication. Administration of methylcobalamin doses greater than 10mcg daily, may produce a hematological response in patients with late deficiency. It is important to monitor methylcobalamin concentrations in plasma and to obtain peripheral blood counts at intervals of 3 to 6 months to confirm the adequacy of therapy.

Since refractoriness to therapy can develop at any time, evaluation must continue throughout the patient's life. Serum concentrations may be decreased by concurrent administration of oral contraceptives. Blood concentrations of methylcobalamin may be reduced if large doses of folate are taken continuously.

Adverse Effects Of Biopentin

The most commonly reported adverse effects associated with gabapentin are somnolence, dizziness, ataxia and fatigue. Nystagmus, tremor, diplopia, amblyopia, pharyngitis, weakness, arthralgia, paresthesia, purpura, leukopenia anxiety and UTI may occur less frequently. Rarely is pancreatitis, altered liver function tests, rhinitis, nervousness, myalgia, headache, nauseous and vomiting have been reported.

Methylcobalamin has no side effects or toxic effects even at high doses for long term.

Dosage and Administration Of Biopentin

Biopentin is given orally with or without food.

If dose is reduced, discontinued or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

The general recommended therapy is to start as one tablet per day on day 1, one tablet each two times a day on day 2, and one tablet each three times a day on day 3. The dose may then be uptitrated up to one tablet each three times a day. The average effective dose of methylcobalamin has been found to be 1500mcg/day which is achieved by giving at least 3 tablets per day.

Overdose

Acute, life-threatening toxicity has not been observed with Gabapentin overdoses of up to 49 grams ingested at one time. In these cases, dizziness, double vision, slurred speech, drowsiness, lethargy and mild diarrhea were observed. All patients recovered with supportive care.

Gabapentin can be removed by hemodialysis. Although hemodialysis has not been performed in the few overdose cases reported, it may be indicated by the patient's clinical state or in patients with significant renal impairment.

Methylcobalamin for clinical effectiveness is 0.5-6 mg/day and no significant therapeutic advantage is observed beyond this range.

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