Methyl G

Uses

Gabapentin is used for-

• Epilepsy
• Neuropathic pain (e.g. postherpetic neuralgia) and other pain conditions
• Bipolar disorder
• Headache syndrome
• Spasticity in multiple sclerosis and spinal cord diseases

Others indication are:

• Alcohol withdrawal
• Schizoaffective disorder
• Post-traumatic stress disorder
• Agitation and behavioural disturbances
• associated with dementia
• Lesch-Nyhan syndrome
• Essential tremor
• Restless legs syndrome
• Brachioradial pruritus
• Hemichorea/hemiballismus
• Hot Flashes

Mecobalamin is used for-

• Peripheral Neuropathies
• Diabetic Neuropathy
• Verteberal Syndrome
• Nerve Compression Syndrome
• Multiple sclerosis
• Amyotrophic lateral sclerosis
• Parkinson’s disease
• Alzheimer’s disease
• Diabetic retinopathy
• Entrapment neuropathy
• Drug induced neuropathy
• Megaloblastic anemia due to Vitamin B12 deficiency

Methyl G is also used to associated treatment for these conditions: Partial-Onset Seizures, Peripheral Neuropathic Pain, Postherpetic NeuralgiaVitamin B12 Deficiency, Nutritional supplementation

How Methyl G works

The precise mechanism through which gabapentin exerts its therapeutic effects is unclear. The primary mode of action appears to be at the auxillary α2δ-1 subunit of voltage-gated calcium channels (though a low affinity for the α2δ-2 subunit has also been reported). The major function of these subunits is to facilitate the movement of pore-forming α1 subunits of calcium channels from the endoplasmic reticulum to the cell membrane of pre-synaptic neurons. There is evidence that chronic pain states can cause an increase in the expression of α2δ subunits and that these changes correlate with hyperalgesia. Gabapentin appears to inhibit the action of α2δ-1 subunits, thus decreasing the density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters. It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin.

There is some evidence that gabapentin also acts on adenosine receptors and voltage-gated potassium channels, though the clinical relevance of its action at these sites is unclear.

Dosage

Methyl G dosage

Neuropathic pain: 300 mg on day-1, then 300 mg twice on day-2, then 300 mg thrice on day-3, then increase the dose according to response in steps of 300 mg daily to maximum 1800 mg daily in three divided doses.

Partial seizure/epilepsy: 300 mg on day-1, then 300 mg twice on day-2, then 300 mg thrice on day-3, then increase the dose according to response in steps of 300 mg daily to maximum 2400 mg daily in three divided doses.

In case of children:

• For 3-12 years: 10 to 15 mg/kg, Incase of titration 25-35 mg/kg daily in 3 divided doses.
• Maintenance dose is 900 mg daily (body weight 26-36 Kg) or 1.2 gm daily (body weight 37-50 Kg).

Tablet: The usual adult dosage is one 500 mcg tablet three times daily. The dosage should be adjusted according to the age of patient and the severity of symptoms.

Injection:

• Peripheral neuropathies: The usual adult dosage is one ampoule equivalent to 500 mcg of Mecobalamin, administered intramuscularly or intravenously three times a week.The dosage should be adjusted according to the age of patient and the severity of symptoms.
• Megaloblastic anemia: The usual adult dosage is one ampoule equivalent to 500 mcg of Mecobalamin, administered intramuscularly or intravenously three times a week. After about two months of administration, dosage should be changed to one ampoule equivalent to 500 mcg of Mecobalamin every one to three months as maintenance therapy

Gabapentin can be taken orally with or without food.

Side Effects

Generally Gabapentin is well tolerated but a few side effects like fatigue, dizziness , ataxia, weight gain, peripheral edema, dry mouth and somnolence, may occur. Rarely it may cause fulminate hepatic failure, or aplasticanemia.

Generally Mecobalamin is well tolerated. However, a few side effects like GI discomfort (including anorexia, nausea or diarrhea) & rash may be seen after administration of Mecobalamin.

Toxicity

The oral TDLo of gabapentin in humans is 2.86 mg/kg and the LD₅₀ in rats has been found to be >8000 mg/kg. Symptoms of overdose are consistent with the drug's adverse effect profile and involve CNS depression (e.g. dizziness, drowsiness, slurred speech, lethargy, loss of consciousness) and gastrointestinal symptoms such as diarrhea. Management of overdose should involve symptomatic and supportive treatment. Gabapentin can be removed by hemodialysis - this may be of benefit in some patients, such as those with impaired renal function.

Multi-drug overdoses involving gabapentin, particularly in combination with other CNS depressants such as opioids, can result in coma and death - this possibility should be considered when managing overdosage.

Precaution

Patients should be instructed to take Gabapentin only as prescribed. While using Gabapentin patients should be instructed either not to drive a car or to operate other complex machinery until they have gained sufficient experiences about Gabapentin whether or not it affects their mental and/or motor performance adversely.

The medicine should not be used for months if there is no response at all after its use for a certain period of time.

Interaction

Antacids may reduce the bioavailability of Gabapentin by up to 20%. Cimetidine may alter its reanal excretion. Gabapentin does not interact with other anti-epileptic drug or with oral contraceptive preparations.

Decreased GI tract absorption with neomycin, aminosalicylic acid, H2-blockers and colchicine. Reduced serum concentrations with oral contraceptives. Reduced effects in anaemia with parenteral chloramphenicol.

Volume of Distribution

The apparent volume of distribution of gabapentin after IV administration is 58±6 L. The drug is found in the CSF in concentrations approximately 9-20% of the corresponding plasma concentrations and is secreted into breast milk in concentrations similar to that seen in plasma.

Elimination Route

Absorption of gabapentin is thought to occur solely via facilitated transport by the LAT1 transporter within the intestines. As this process is saturable, the oral bioavailability of gabapentin is inversely proportional to the administered dose - the oral bioavailability of a 900mg/day regimen is approximately 60%, whereas a 4800mg/day regimen results in only 27% bioavailability. The T_max of gabapentin has been estimated to be 2-3 hours. Food has no appreciable effect on gabapentin absorption.

Half Life

The elimination t_1/2 of gabapentin in patients with normal renal function is 5-7 hours. In patients with reduced renal function, the elimination t_1/2 may be prolonged - in patients with a creatinine clearance of 16,17

Clearance

Both the plasma clearance and renal clearance of gabapentin are directly proportional to the patient's creatinine clearance due to its primarily renal elimination.

Elimination Route

Gabapentin is eliminated solely in the urine as unchanged drug. Cimetidine, an inhibitor of renal tubular secretion, reduces clearance by approximately 12%, suggesting that some degree of tubular secretion is involved in the renal elimination of gabapentin.

Pregnancy & Breastfeeding use

Pregnancy: Gabapentin is a pregnancy category C drug; it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Gabapentin may be secreted through the breast milk like many other drugs , so it should be used in women who are nursing, only if the benefits clearly outweigh the risks.

Not recommended during pregnancy & lactation.

Contraindication

Gabapentin is contraindicated in patients who have known hypersensitivity to the drug.

Hypersensitivity to any component of this product.

Special Warning

Use in Children: Safety and effectiveness of Gabapentin in the management of neuropathic pain in pediatric patients have not been established. Safety and effectiveness of Gabapentin in the management of seizures in pediatric patients below the age of 3 years have not been established.

Renal impaired patient: In case of renal impaired patient Gabapentin doses must be reduced :

• CrCl >60 ml/min: 1200 mg/daily in 3 divided doses
• CrCl 30-60 ml/min: 600 mg/daily in 2 divided doses
• CrCl 15-30 ml/min: 300 mg/daily single dose
• CrCl <15 ml/min: 150 mg/daily single dose or 300 mg/every alternate day
• Heamodialysis: maximum 300 mg after each dialysis Gabapentin can be taken orally with or without food.

Use in children: Not recommended.

Storage Condition

Tablets should be stored below 25° C and protected from light & moisture

Oral: Store at room temperature. Protect from moisture and light.

Parenteral: Store at room temperature. Do not expose to direct light.

Innovators Monograph

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