Repligen (ANTIEPILEPTIC)

Uses

Repligen (ANTIEPILEPTIC) 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

Repligen (ANTIEPILEPTIC) is also used to associated treatment for these conditions: Partial-Onset Seizures, Peripheral Neuropathic Pain, Postherpetic Neuralgia

How Repligen (ANTIEPILEPTIC) 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. Repligen (ANTIEPILEPTIC) 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

Repligen (ANTIEPILEPTIC) 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).

Repligen (ANTIEPILEPTIC) can be taken orally with or without food.

Side Effects

Generally Repligen (ANTIEPILEPTIC) 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.

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

Interaction

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

Food Interaction

• Avoid alcohol. Repligen (ANTIEPILEPTIC) possesses CNS depressant activity that may be potentiated by co-administration with alcohol.
• Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

Repligen (ANTIEPILEPTIC) Drug Interaction

Major: acetaminophen / hydrocodone, acetaminophen / hydrocodoneModerate: duloxetine, duloxetine, alprazolam, alprazolamUnknown: aspirin, aspirin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Repligen (ANTIEPILEPTIC) Disease Interaction

Major: drug dependence, renal dysfunctionModerate: suicidal tendency, hemodialysis

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

Repligen (ANTIEPILEPTIC) 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: Repligen (ANTIEPILEPTIC) 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: Repligen (ANTIEPILEPTIC) 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.

Contraindication

Repligen (ANTIEPILEPTIC) is contraindicated in patients who have known hypersensitivity to the drug.

Special Warning

Use in Children: Safety and effectiveness of Repligen (ANTIEPILEPTIC) in the management of neuropathic pain in pediatric patients have not been established. Safety and effectiveness of Repligen (ANTIEPILEPTIC) 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 Repligen (ANTIEPILEPTIC) 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 Repligen (ANTIEPILEPTIC) can be taken orally with or without food.

Storage Condition

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

Innovators Monograph

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