Actions of Dygab in details
Pharmacology: Dygab is a γ-aminobutyric acid analogue.
Mechanism of Action: Dygab binds with high affinity to the α2-δ site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of Dygab is unknown, results with genetically modified mice and with compounds structurally related to Dygab suggest that binding to the α -δ subunit may be involved in Dygab's antinociceptive and antiseizure effects in animal models.
While Dygab is a structural derivative of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation.
Pharmacokinetics: Dygab is well-absorbed after oral administration, is eliminated largely by renal excretion and has an elimination half-life (t½) of about 6 hrs. Following oral administration of Dygab capsules under fasting conditions, peak plasma concentrations occur within 1.5 hrs. Dygab oral bioavailability is >90% and is independent of dose. Following single (25-300 mg) and multiple dose (75-900 mg/day) administration, maximum plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady-state is achieved within 24-48 hrs. Multiple-dose pharmacokinetics can be predicted from single-dose data.
The rate of Dygab absorption is decreased when given with food, resulting in a decrease in Cmax of approximately 25-30% and an increase in time to reach maximum plasma concentration (Tmax) to approximately 3 hrs. However, administration of maxpregabalin with food has no clinically relevant effect on the total absorption of Dygab. Therefore, Dygab can be taken with or without food. Dygab does not bind to plasma proteins. The apparent volume of distribution of Dygab following oral administration is approximately 0.5 L/kg.
Dygab undergoes negligible metabolism in humans. Following a dose of radiolabeled Dygab, approximately 90% of the administered dose was recovered in the urine as unchanged Dygab. The N-methylated derivative of Dygab, the major metabolite of Dygab found in urine, accounted for 0.9% of the dose.
Dygab is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination t½ of 6.3 hrs in subjects with normal renal function. Mean renal clearance was estimated to be 67-80.9 mL/min in young healthy subjects. Because Dygab is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Dygab elimination is nearly proportional to creatinine clearance (CrCl). No specific pharmacokinetic studies were carried out in patients with impaired liver function. Since Dygab does not undergo significant metabolism and is excreted predominantly as unchanged drug in the urine, impaired liver function would not be expected to significantly alter Dygab plasma concentrations.
Dygab oral clearance tended to decrease with increasing age. This decrease in Dygab oral clearance is consistent with age-related decreases in CrCl. Pharmacokinetics of Dygab have not been adequately studied in pediatric patients.
How should I take Dygab?
Take Dygab exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
You may take Dygab with or without food.
Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
Do not change your dose of Dygab without your doctor's advice. Tell your doctor if the medication does not seem to work as well in treating your condition.
Call your doctor if you have any problems with your vision while taking Dygab. If you are taking Dygab to prevent seizures, keep taking it even if you feel fine. You may have an increase in seizures if you stop taking Dygab. Follow your doctor's instructions. Do not stop using Dygab without first talking to your doctor, even if you feel fine. You may have increased seizures or withdrawal symptoms such as headache, sleep problems, nausea, and diarrhea. Ask your doctor how to avoid withdrawal symptoms when you stop using Dygab. Wear a medical alert tag or carry an ID card stating that you take Dygab. Any medical care provider who treats you should know that you take seizure medication.
Store at room temperature away from moisture, light, and heat.
Dygab administration
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
You may take Dygab with or without food.
Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
Do not change your dose of Dygab without your doctor's advice. Tell your doctor if the medication does not seem to work as well in treating your condition.
Call your doctor if you have any problems with your vision while taking Dygab.
If you are taking Dygab to prevent seizures, keep taking it even if you feel fine. You may have an increase in seizures if you stop taking Dygab. Follow your doctor's instructions.
Do not stop using Dygab without first talking to your doctor, even if you feel fine. You may have increased seizures or withdrawal symptoms such as headache, sleep problems, nausea, and diarrhea. Ask your doctor how to avoid withdrawal symptoms when you stop using Dygab.
Wear a medical alert tag or carry an ID card stating that you take Dygab. Any medical care provider who treats you should know that you take seizure medication.
Store at room temperature away from moisture, light, and heat.
Dygab pharmacology
Mechanism of Action
Dygab (Dygab) binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of Dygab has not been fully elucidated, results with genetically modified mice and with compounds structurally related to Dygab (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in Dygab's anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, Dygab has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha2-delta containing-calcium channel trafficking and/or reducing calcium currents. Evidence from other animal models of nerve damage and persistent pain suggest the anti-nociceptive activities of Dygab may also be mediated through interactions with descending noradrenergic and serotonergic pathways originating from the brainstem that modulate pain transmission in the spinal cord.
While Dygab is a structural derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of Dygab increases the density of GABA transporter protein and increases the rate of functional GABA transport. Dygab does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Pharmacokinetics
Dygab is well absorbed after oral administration, is eliminated largely by renal excretion, and has an elimination half-life of about 6 hours.
Absorption and Distribution
Following oral administration of Dygab capsules under fasting conditions, peak plasma concentrations occur within 1.5 hours. Dygab oral bioavailability is ≥90% and is independent of dose. Following single- (25 to 300 mg) and multiple- dose (75 to 900 mg/day) administration, maximum plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC) values increase linearly. Following repeated administration, steady state is achieved within 24 to 48 hours. Multiple-dose pharmacokinetics can be predicted from single-dose data.
The rate of Dygab absorption is decreased when given with food, resulting in a decrease in Cmax of approximately 25% to 30% and an increase in Tmax to approximately 3 hours. However, administration of Dygab with food has no clinically relevant effect on the total absorption of Dygab. Therefore, Dygab can be taken with or without food.
Dygab does not bind to plasma proteins. The apparent volume of distribution of Dygab following oral administration is approximately 0.5 L/kg. Dygab is a substrate for system L transporter which is responsible for the transport of large amino acids across the blood brain barrier. Although there are no data in humans, Dygab has been shown to cross the blood brain barrier in mice, rats, and monkeys. In addition, Dygab has been shown to cross the placenta in rats and is present in the milk of lactating rats.
Metabolism and Elimination
Dygab undergoes negligible metabolism in humans. Following a dose of radiolabeled Dygab, approximately 90% of the administered dose was recovered in the urine as unchanged Dygab. The N-methylated derivative of Dygab, the major metabolite of Dygab found in urine, accounted for 0.9% of the dose. In preclinical studies, Dygab (S-enantiomer) did not undergo racemization to the R-enantiomer in mice, rats, rabbits, or monkeys.
Dygab is eliminated from the systemic circulation primarily by renal excretion as unchanged drug with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67.0 to 80.9 mL/min in young healthy subjects. Because Dygab is not bound to plasma proteins this clearance rate indicates that renal tubular reabsorption is involved. Dygab elimination is nearly proportional to creatinine clearance (CLcr).
Pharmacokinetics in Special Populations
Race
In population pharmacokinetic analyses of the clinical studies in various populations, the pharmacokinetics of Dygab were not significantly affected by race (Caucasians, Blacks, and Hispanics).
Gender
Population pharmacokinetic analyses of the clinical studies showed that the relationship between daily dose and Dygab drug exposure is similar between genders.
Renal Impairment and Hemodialysis
Dygab clearance is nearly proportional to creatinine clearance (CLcr). Dosage reduction in patients with renal dysfunction is necessary. Dygab is effectively removed from plasma by hemodialysis. Following a 4-hour hemodialysis treatment, plasma Dygab concentrations are reduced by approximately 50%. For patients on hemodialysis, dosing must be modified.
Elderly
Dygab oral clearance tended to decrease with increasing age. This decrease in Dygab oral clearance is consistent with age-related decreases in CLcr. Reduction of Dygab dose may be required in patients who have age-related compromised renal function.
Pediatric Pharmacokinetics
Pharmacokinetics of Dygab have not been adequately studied in pediatric patients.
Drug Interactions
In Vitro Studies
Dygab, at concentrations that were, in general, 10-times those attained in clinical trials, does not inhibit human CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 enzyme systems. In vitro drug interaction studies demonstrate that Dygab does not induce CYP1A2 or CYP3A4 activity. Therefore, an increase in the metabolism of coadministered CYP1A2 substrates (e.g. theophylline, caffeine) or CYP 3A4 substrates (e.g., midazolam, testosterone) is not anticipated.
In Vivo Studies
The drug interaction studies described in this section were conducted in healthy adults, and across various patient populations.
Gabapentin
The pharmacokinetic interactions of Dygab and gabapentin were investigated in 12 healthy subjects following concomitant single-dose administration of 100-mg Dygab and 300-mg gabapentin and in 18 healthy subjects following concomitant multiple-dose administration of 200-mg Dygab every 8 hours and 400-mg gabapentin every 8 hours. Gabapentin pharmacokinetics following single- and multiple-dose administration were unaltered by Dygab coadministration. The extent of Dygab absorption was unaffected by gabapentin coadministration, although there was a small reduction in rate of absorption.
Oral Contraceptive
Dygab coadministration (200 mg three times a day) had no effect on the steady-state pharmacokinetics of norethindrone and ethinyl estradiol (1 mg/35 µg, respectively) in healthy subjects.
Lorazepam
Multiple-dose administration of Dygab (300 mg twice a day) in healthy subjects had no effect on the rate and extent of lorazepam single-dose pharmacokinetics and single-dose administration of lorazepam (1 mg) had no effect on the steady-state pharmacokinetics of Dygab.
Oxycodone
Multiple-dose administration of Dygab (300 mg twice a day) in healthy subjects had no effect on the rate and extent of oxycodone single-dose pharmacokinetics. Single-dose administration of oxycodone (10 mg) had no effect on the steady-state pharmacokinetics of Dygab.
Ethanol
Multiple-dose administration of Dygab (300 mg twice a day) in healthy subjects had no effect on the rate and extent of ethanol single-dose pharmacokinetics and single-dose administration of ethanol (0.7 g/kg) had no effect on the steady-state pharmacokinetics of Dygab.
Phenytoin, carbamazepine, valproic acid, and lamotrigine
Steady-state trough plasma concentrations of phenytoin, carbamazepine and carbamazepine 10,11 epoxide, valproic acid, and lamotrigine were not affected by concomitant Dygab (200 mg three times a day) administration.
Population pharmacokinetic analyses in patients treated with Dygab and various concomitant medications suggest the following:
| Therapeutic class | Specific concomitant drug studied |
|---|---|
| Concomitant drug has no effect on the pharmacokinetics of Dygab | |
| Hypoglycemics | Glyburide, insulin, metformin |
| Diuretics | Furosemide |
| Antiepileptic Drugs | Tiagabine |
| Concomitant drug has no effect on the pharmacokinetics of Dygab and Dygab has no effect on the pharmacokinetics of concomitant drug | |
| Antiepileptic Drugs | Carbamazepine, lamotrigine, phenobarbital, phenytoin, topiramate, valproic acid |
References
- DailyMed. "PREGABALIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Pregabalin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Pregabalin: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Dygab are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Dygab. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported administration
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Information checked by Dr. Sachin Kumar, MD Pharmacology
