Gabapentin enacarbil
Gabapentin enacarbil Uses, Dosage, Side Effects, Food Interaction and all others data.
Gabapentin enacarbil is an anti-convulsant. It is a structural analog of gamma-amino-butyric-acid (GABA). All pharmacological actions following administration of Gabapentin enacarbil are due to the activity of parent compound. Gabapentin enacarbil binds with the alpha-2-delta subunit of voltage gated L-type Calcium channel, and inhibits branched chain amino acid transferase & probably inhibits neurotransmitter release of excitatory amino acid.
Gabapentin enacarbil is an anti-convulsant medication that inhibits the release of excitatory neurotransmitters, allowing for its use against pathologic neurotransmission such as that seen in neuropathic pain and seizure disorders. It has a wide therapeutic index, with doses in excess of 8000 mg/kg failing to cause a fatal reaction in rats.
Gabapentin enacarbil is ineffective in absence seizures and should be used in caution in patients with mixed seizure disorders involving absence seizures. Gabapentin enacarbil has been associated with drug reaction with eosinophilia and systemic symptoms (DRESS), otherwise known as multi-organ hypersensitivity. This reaction can prove fatal and early symptoms such as fever, lymphadenopathy, and rash should be promptly investigated.
| Trade Name | Gabapentin enacarbil |
| Availability | Prescription only |
| Generic | Gabapentin |
| Gabapentin Other Names | Gabapentin, Gabapentina, Gabapentine, Gabapentino, Gabapentinum |
| Related Drugs | clonazepam, lamotrigine, pregabalin, Lyrica, topiramate, levetiracetam, lidocaine topical, Neurontin, Lidoderm, capsaicin topical |
| Type | Oral |
| Formula | C9H17NO2 |
| Weight | Average: 171.2368 Monoisotopic: 171.125928793 |
| Protein binding | Less than 3% of an orally administered dose of gabapentin is bound to plasma proteins. |
| Groups | Approved, Investigational |
| Therapeutic Class | Adjunct anti-epileptic drugs |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Gabapentin enacarbil 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
Gabapentin enacarbil is also used to associated treatment for these conditions: Partial-Onset Seizures, Peripheral Neuropathic Pain, Postherpetic Neuralgia
How Gabapentin enacarbil 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 enacarbil 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
Gabapentin enacarbil 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).
Gabapentin enacarbil can be taken orally with or without food.
Side Effects
Generally Gabapentin enacarbil 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. Gabapentin enacarbil 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 enacarbil only as prescribed. While using Gabapentin enacarbil patients should be instructed either not to drive a car or to operate other complex machinery until they have gained sufficient experiences about Gabapentin enacarbil whether or not it affects their mental and/or motor performance adversely.
Interaction
Antacids may reduce the bioavailability of Gabapentin enacarbil by up to 20%. Cimetidine may alter its reanal excretion. Gabapentin enacarbil does not interact with other anti-epileptic drug or with oral contraceptive preparations.
Food Interaction
- Avoid alcohol. Gabapentin enacarbil 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.
Gabapentin enacarbil 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
Gabapentin enacarbil 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 Tmax of gabapentin has been estimated to be 2-3 hours. Food has no appreciable effect on gabapentin absorption.
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 enacarbil 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 enacarbil 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 enacarbil 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
Gabapentin enacarbil is contraindicated in patients who have known hypersensitivity to the drug.
Special Warning
Use in Children: Safety and effectiveness of Gabapentin enacarbil in the management of neuropathic pain in pediatric patients have not been established. Safety and effectiveness of Gabapentin enacarbil 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 enacarbil 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 enacarbil 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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FAQ
What is Gabapentin enacarbil used to treat?
Gabapentin enacarbil is used to treat epilepsy. It's also taken for nerve pain. Nerve pain can be caused by different illnesses, including diabetes and shingles, or it can happen after an injury.
Is Gabapentin enacarbil considered a painkiller?
Gabapentin enacarbil is a prescription painkiller belonging to its own drug class, Gabapentinoids. It is considered an anti-convulsant, and is most commonly used to treat epilepsy, restless leg syndrome, hot flashes, and neuropathic pain.
What is the most common side effect of Gabapentin enacarbil?
The most common side effects are Drowsiness, dizziness, loss of coordination, tiredness, blurred/double vision, unusual eye movements, or shaking (tremor).
How does Gabapentin enacarbil make my feel?
Gabapentin enacarbil can produce feelings of relaxation, calmness and euphoria. Some users have reported that the high from snorted Gabapentin enacarbil can be similar to taking a stimulant. It can also enhance the euphoric effects of other drugs, like heroin and other opioids, and is likely to increase the risks when taken in this way.
Why is Gabapentin enacarbil bad?
Gabapentin enacarbil may interact with certain types of substances and cause negative side effects. For example, mixing alcohol and gabapentin can cause people to feel dizzy or tired. Despite the risk of bad side effects of using Gabapentin enacarbil, it can be more dangerous to stop using it. Gabapentin enacarbil use can cause physical dependence.
Can I drink coffee with Gabapentin enacarbil?
In addition, Gabapentin enacarbil can interact with caffeine and diminish its anticonvulsant effects (mice studies).
Does Gabapentin enacarbil help to sleep?
Gabapentin enacarbil enhances slow-wave sleep in patients with primary insomnia. It also improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal. Gabapentin enacarbil may be beneficial in the treatment of primary insomnia.
Is Gabapentin enacarbil a muscle relaxer?
Gabapentin enacarbil is an anticonvulsive medication that originally saw use as a muscle relaxer and anti-spasmodic medication, but later it was discovered it had the potential of the medication as anticonvulsive medication and as an adjunct to more potent anticonvulsants.
How long does Gabapentin enacarbil take to work?
Peak concentrations of Gabapentin enacarbil (immediate-release) occur within 2 to 3 hours. Although Gabapentin enacarbil may improve sleep problems due to nerve pain within a week, it may take up to two weeks for symptom relief from nerve pain to occur.
Who should not take Gabapentin enacarbil?
The following conditions are contraindicated with this Gabapentin enacarbil. Check with your physician if you have any of the following Conditions:
- suicidal thoughts
- depression
- myasthenia gravis, a skeletal muscle disorder
- decreased lung function
- chronic obstructive pulmonary disease
- chronic kidney disease
- kidney disease with likely reduction in kidney function
What vitamins should not be taken with Gabapentin enacarbil?
Avoid taking aluminum or magnesium containing products (such as antacids) for 2 hours before your Gabapentin enacarbil. If you notice any signs of seizures, including abnormal auras or motor movements, contact your healthcare professional (e.g. doctor or pharmacist).
Should I eat before taking Gabapentin enacarbil?
You can take Gabapentin enacarbil with or without food. But wait at least two hours after taking an antacid that contains magnesium, calcium or aluminum before taking your gabapentin dose.
Is Gabapentin enacarbil safe for seniors?
Gabapentin enacarbil is an effective treatment for chronic neuropathic pain but may cause dizziness, drowsiness, and confusion in some older adults.
Does Gabapentin enacarbil help with anxiety?
Gabapentin enacarbil is considered an off-Gabapentin enacarbil drug used to treat anxiety. Gabapentin enacarbil has shown to help people with sleeping better, as insomnia is a symptom of anxiety.
How safe is Gabapentin enacarbil?
Gabapentin enacarbil is a fairly safe medication when people take it according to a doctor's instructions. However, some people may experience side effects. Common side effects that generally do not require medical attention include: blurred vision.
What happens when I stop Gabapentin enacarbil?
Symptoms of Gabapentin enacarbil withdrawal may include nausea, dizziness, headaches, insomnia, and anxiety. The safest way to stop using Gabapentin enacarbil is to taper off the medication under the supervision of a doctor.
Does Gabapentin enacarbil help with depression?
There is no clear evidence for Gabapentin enacarbil therapy in depression, PTSD prevention, OCD, or other types of substance abuse.
Does Gabapentin enacarbil raise my blood pressure?
High blood pressure is not a common side effect from Gabapentin enacarbil. However, if a patient is abruptly withdrawn from Gabapentin enacarbil and they are using it to control nerve pain, the pain can abruptly return. Severe pain in and of itself can drive up blood pressure.
What drugs should not be taken with Gabapentin enacarbil?
Gabapentin enacarbil can interact with losartan, ethacrynic acid, caffeine, phenytoin, mefloquine, magnesium oxide, cimetidine, naproxen, sevelamer and morphine. Gabapentin enacarbil use is contraindicated in patients with myasthenia gravis or myoclonus.
How does Gabapentin enacarbil work?
Gabapentin enacarbil appears to work by altering electrical activity in the brain and influencing the activity of chemicals called neurotransmitters, which send messages between nerve cells.
How long does it take for Gabapentin enacarbil to work?
You should notice that your pain starts to improve over one to two weeks after starting Gabapentin enacarbil, but it may take longer in some people. However, some feel benefit straight away. Your treatment will be reviewed when you next see the doctor or nurse.
How long does Gabapentin enacarbil last?
The half-life of Gabapentin enacarbil in most people will range from five to seven hours.
How long does Gabapentin enacarbil stay in our system?
The detectability of Gabapentin enacarbil will range from five to seven hours for most blood tests. It is undetectable in saliva swab tests. Hair tests might be able to specifically detect the presence of Gabapentin enacarbil for up to 90 days; however, it would be highly unusual for a hair test to be used to detect Gabapentin enacarbil.
What are the risks of taking Gabapentin enacarbil?
Gabapentin enacarbil may cause
- abnormal eye movements that are continuous, uncontrolled, back-and-forth, or rolling.
- clumsiness or unsteadiness.
- constipation.
- diarrhea.
- difficulty speaking.
- drowsiness or tiredness.
- dry mouth.
- nausea.
What are the long term effects of taking Gabapentin enacarbil?
People with preexisting kidney disease may experience potentially fatal toxicity when taking Gabapentin enacarbil. Gabapentin enacarbil may cause other long-term effects, including memory loss, weakened muscles, and respiratory failure.
Why is Gabapentin enacarbil bad?
Gabapentin enacarbil may interact with certain types of substances and cause negative side effects. For example, mixing alcohol and Gabapentin enacarbil can cause people to feel dizzy or tired. Despite the risk of bad side effects of using Gabapentin enacarbil, it can be more dangerous to stop using it. Gabapentin enacarbil use can cause physical dependence.
How to I stop taking Gabapentin enacarbil?
The timeline to reduce Gabapentin enacarbil depends on the individual and the current dose of the medication. Your doctor will develop a plan to slowly take you off the medication. This could be lowering the dose over a week or over several weeks.
