Pregabalin Capsules

Pharmacological action Pregabalin has a high affinity for the α2-δ site (an auxiliary subunit of voltage-gated calcium channels) in the central nervous system. The mechanism of action of pregabalin is still unclear, but the results of studies on transgenic mice and structurally related compounds (such as gabapentin) suggest that the analgesic and anticonvulsant effects in animal models may be related to the binding of pregabalin to the α2-δ subunit. In vitro studies have shown that pregabalin may reduce the calcium-dependent release of some neurotransmitters by regulating calcium channel function. Although pregabalin is a structural derivative of the inhibitory neurotransmitter g-aminobutyric acid (GABA), it does not directly bind to GABAA, GABAB or benzodiazepine receptors, does not increase the GABAA response of neurons cultured in vitro, does not change the GABA concentration in the rat brain, and has no acute effect on GABA uptake or degradation. However, studies have found that long-term exposure of neurons cultured in vitro to pregabalin increases the density of GABA transporters and the rate of functional GABA transport. Pregabalin does not block sodium channels, is inactive at opioid receptors, does not alter cyclooxygenase activity, is inactive at dopamine and 5-hydroxytryptamine receptors, and does not inhibit the reuptake of dopamine, 5-hydroxytryptamine, or norepinephrine. Genotoxicity: In vitro studies have shown that pregabalin has no mutagenic effect on bacteria and mammalian cells. In vivo and in vitro studies have shown that pregabalin does not cause mammalian chromosome aberrations and does not induce unscheduled DNA synthesis in hepatocytes in rats or mice. Reproductive toxicity: Male rats orally administered pregabalin (50 to 2500 mg/kg) before and during mating, mated with untreated female rats, and multiple adverse effects on reproduction and development were observed, including decreased sperm count, decreased sperm motility, increased sperm abnormalities, decreased fertility, increased preimplantation loss rate, reduced litter size, decreased fetal weight, and increased incidence of fetal abnormalities. The effects on sperm and fertility parameters were reversible during the study period (3-4 months). At the no-effect dose (100 mg/kg) for reproduction in male rats, the exposure (AUC) of plasma pregabalin was approximately 3 times the human exposure at the maximum recommended clinical dose (MRD). In addition, in general toxicity studies of 4 weeks or longer, adverse reactions to reproductive organs (testes, epididymis) were observed in male rats at doses of 500-1250 mg/kg by histopathological examination, and the no-effect dose was 250 mg/kg, which was approximately 8 times the human plasma exposure at the MRD. Female rats were orally given pregabalin at 500, 1250, and 2500 mg/kg before mating, during mating, and in early pregnancy. Estrous cycle disorders and increased mating days were observed at each dose, and embryonic death was observed at high doses. The plasma exposure of pregabalin at low doses was approximately 9 times the exposure at the human MRD, and the no-effect dose has not been determined. Increased incidence of fetal structural malformations and other developmental toxicities, including fetal mortality, growth retardation, and impairment of neurological and reproductive function, were observed in pregnant rats and rabbits at plasma pregabalin exposures (AUC) equivalent to ≥5 times the MRD. Pregnant rats were given pregabalin orally at 500, 1250, or 2500 mg/kg during organogenesis, and plasma pregabalin exposures (AUC) at the low dose were approximately 17 times the human exposure at the MRD. At doses ≥1250 mg/kg, there was an increased incidence of specific skull abnormalities due to abnormal premature ossification (premature fusion of the zygomatic and nasal sutures). Skeletal variations and delayed ossification were observed at all doses. Fetal body weights were reduced at high doses. A no-effect dose for pregabalin on embryo-fetal development in rats has not been established. Pregnant rabbits were given pregabalin orally at 250, 500, or 1250 mg/kg during organogenesis. At high doses, reduced fetal weight, delayed ossification, increased incidence of skeletal deformities and visceral variations can be seen. The no-effect dose for rabbit development is 500 mg/kg, and the plasma exposure is approximately 16 times the human exposure at MRD. In the perinatal toxicity test, rats were orally given pregabalin at 50, 100, 250, 1250 or 2500 mg/kg. The growth of the offspring slowed down at ≥100 mg/kg, and the survival rate of the offspring decreased at ≥250 mg/kg. There was a significant effect on the survival rate of the offspring at ≥1250 mg/kg, and the mortality rate of the litter was 100% at the highest dose. When the offspring were tested after adulthood, neurobehavioral abnormalities (reduced auditory startle response) were observed at ≥250 mg/kg, and reproductive function impairment (reduced fertility and reduced litter size) was observed at 1250 mg/kg. The no-effect dose for rat perinatal development was 50 mg/kg, and the plasma exposure was approximately twice the human exposure at MRD. Carcinogenicity: B6C3F1 and CD-1 mice were given pregabalin 200, 1000, 5000 mg/kg by diet for 2 consecutive years, and the incidence of vascular malignant tumors (angiosarcoma) increased in a dose-dependent manner. The plasma pregabalin exposure (AUC) of mice at the lowest dose was approximately equivalent to the exposure at the MRD, and the no-effect dose for induction of angiosarcoma in mice has not yet been determined. Wistar rats were given pregabalin by diet for 2 consecutive years, with male rats at doses of 50, 150, and 450 mg/kg and female rats at doses of 100, 300, and 900 mg/kg. The highest doses were equivalent to 14 times and 24 times the human exposure at the MRD, respectively, and no increase in tumor incidence was observed. Other toxicities Skin toxicity Skin lesions were observed in repeated dosing toxicity tests in rats and monkeys, with lesions ranging from erythema to necrosis, and the cause is still unclear. The dose of pregabalin that causes skin lesions is twice the MRD. More severe skin lesions, including necrosis, occurred at plasma pregabalin exposures (AUC) 3–8 times the human exposure at the MRD. No increased incidence of skin lesions was observed in clinical trials. Ocular Lesions Ocular lesions (characterized by retinal atrophy [including loss of photoreceptor cells] and/or corneal inflammation/mineral deposition) were observed in two Wistar rat carcinogenicity studies at plasma pregabalin exposures (AUC) ≥2 times the human exposure at the MRD, and no effect dose was established. Similar lesions were not observed in the 2-year carcinogenicity study in two strains of mice or in the 1-year carcinogenicity study in monkeys.

The main ingredient of this product is pregabalin, and its chemical name is (S)-3-(aminomethyl)-5-methylhexanoic acid. Molecular formula: C8H17NO2 Molecular weight: 159.23

The content of this product is white to off-white powder.

This product is used to treat: Postherpetic neuralgia Fibromyalgia

This product can be taken with or without food. For the treatment of postherpetic neuralgia: The recommended dose of this product is 75 or 150 mg twice a day, or 50 mg or 100 mg three times a day. The starting dose can be 75 mg twice a day, or 50 mg three times a day. It can be increased to 150 mg twice a day within one week based on efficacy and tolerability. Since this product is mainly excreted by the kidneys, the dose should be adjusted for patients with impaired renal function. The above recommended doses are suitable for patients with creatinine clearance ≥ 60 ml/min. Patients who do not get adequate pain relief after taking 300 mg/day of this product for 2 to 4 weeks can increase the dose to 300 mg twice a day, or 200 mg three times a day (600 mg/day) if they can tolerate this product. Since adverse reactions are dose-dependent and adverse reactions can lead to a higher discontinuation rate, doses exceeding 300 mg/day should only be used for patients with persistent pain who can tolerate a dose of 300 mg/day (see [Adverse Reactions]). Treatment of fibromyalgia: The recommended dose of this product for the treatment of fibromyalgia is 300 to 450 mg/day. The starting dose should be 75 mg each time, twice a day (150 mg/day), which can be increased to 150 mg twice a day (300 mg/day) within one week based on efficacy and tolerability. Patients who do not benefit sufficiently from 300 mg/day can increase to 225 mg twice a day (450 mg/day). Although clinical trials have used 600 mg/day of this product, there is no evidence that this dose has additional significant efficacy benefits, and this dose is poorly tolerated. Considering the dose-dependency of adverse reactions, it is not recommended to exceed 450 mg/day (see [Adverse Reactions]). Since this product is mainly excreted by the kidneys, the dose should be adjusted for patients with impaired renal function (see [Dosage and Administration]). If pregabalin needs to be discontinued, it is recommended to gradually reduce it over at least 1 week. Use in patients with renal impairment: Because adverse reactions are dose-dependent and this product is primarily excreted by the kidneys, the dose should be adjusted in patients with impaired renal function. The dose should be adjusted in patients with renal impairment based on creatinine clearance (CLcr), as detailed in Table 1. When using this table, it is necessary to estimate the patient's CLcr (in milliliters per minute). CLcr (in milliliters per minute) can be calculated by measuring the plasma creatinine level (in mg/dL) and substituting it into the Cockcroft and Gault equation. For patients undergoing hemodialysis, the daily dose of pregabalin should be adjusted based on the patient's renal function. In addition to adjusting the daily dose, a supplemental dose of pregabalin should be given immediately after every 4 hours of hemodialysis treatment (see Table 1). Table 1. Adjustment of pregabalin dose based on renal function Use in patients with hepatic impairment: No dose adjustment is required for patients with hepatic impairment (see [Pharmacokinetics]).

Experience from clinical trials: Because clinical trials are conducted under a variety of different circumstances, it is not possible to directly compare the incidence of adverse reactions of one drug with another in different clinical trials, and the incidence may not represent the incidence observed in clinical practice. In all premarketing controlled and uncontrolled trials of pregabalin, more than 10,000 patients from different populations took this product. Approximately 5,000 people took the drug for at least 6 months, more than 3,100 people took the drug for at least 1 year, and more than 1,400 people took the drug for at least 2 years. The most common adverse reaction leading to discontinuation in all premarketing controlled trials Integrating the data of all populations in premarketing controlled trials, the proportion of patients who discontinued the drug prematurely due to adverse reactions was 14% and 7% in the pregabalin and placebo groups, respectively. The most common adverse reactions leading to discontinuation of pregabalin were dizziness (4%) and somnolence (3%). 1% of patients in the placebo group discontinued the drug due to dizziness,

Those who are allergic to the active ingredients or any excipients contained in this product.

Precautions for children: The safety and effectiveness of the drug for children and adolescents under 18 years of age have not been established, and this product is not recommended. Precautions for pregnancy and lactation: Animal studies have shown that this product has reproductive toxicity. (See [Pharmacology and Toxicology]). The possible risks of this product to humans are currently unknown. There is no clinical data on the effect of this product on female fertility. In a clinical trial evaluating the effect of this product on sperm motility, healthy male subjects were exposed to a dose of 600 mg/day of this product. After 3 months of administration, no effect on sperm motility was found. There is insufficient data on the use of pregabalin in pregnant women. Unless necessary (the benefits of taking the drug for pregnant women clearly outweigh the potential risks of the drug to the fetus), this product should not be taken during pregnancy. Women of childbearing age must use effective contraceptive measures. Pregabalin can be secreted into human milk (see [Precautions]). The effects of pregabalin on newborns/infants are unclear. The benefits of breastfeeding to the child and the benefits of treatment to the mother must be considered to decide whether to stop breastfeeding or stop pregabalin treatment. Elderly precautions: Elderly patients may need to reduce the dosage due to decreased renal function (see [Dosage and Administration] Medication for Patients with Impaired Renal Function). In a controlled clinical study of pregabalin for the treatment of postherpetic neuralgia, there were 282 patients aged 65 to 74 years and 379 patients aged 75 years and above. No overall difference in safety and efficacy was observed between the elderly and younger patients. In a controlled clinical study of pregabalin for the treatment of fibromyalgia, there were 106 patients aged 65 years and above. Although the adverse reactions in the two age groups were similar, the incidence of the following neurological adverse reactions was higher in the group over 65 years old: dizziness, blurred vision, balance disorders, tremor, confusion, abnormal coordination, and drowsiness.

Since pregabalin is mainly excreted in the urine as unchanged drug, its metabolism in humans can be ignored (less than 2% of the administered dose of drug metabolites were found in the urine). In vitro studies have shown that pregabalin does not inhibit drug metabolism and does not bind to plasma proteins, and pregabalin has almost no pharmacokinetic interactions with other drugs. Similarly, no clinically relevant pharmacokinetic interactions between pregabalin and phenytoin, carbamazepine, valproic acid, lamotrigine, gabapentin, lorazepam, oxycodone or ethanol were observed in animal studies. Population pharmacokinetic analysis showed that oral antidiabetic drugs, diuretics, insulin, phenobarbital, tiagabine and topiramate had no significant clinical effect on the clearance of pregabalin. When pregabalin was taken with the oral contraceptives norethindrone and/or ethinyl estradiol, the steady-state pharmacokinetics of both substances were not affected. Pregabalin may enhance the effects of ethanol and lorazepam. In controlled clinical studies, when multiple oral doses of pregabalin were combined with oxycodone, lorazepam, or ethanol, no clinically significant effects on the patient's respiration were observed. Post-marketing reports of respiratory failure and coma have been reported with the combination of pregabalin and centrally acting antidepressants. Pregabalin can enhance cognitive dysfunction and overall motor dysfunction caused by oxycodone. Drug interaction studies have only been conducted in adults, not specifically in elderly volunteers.

Keep sealed.

75 mg x 8 capsules x 4 plates

24 months

Qilu Pharmaceutical (Hainan) Co., Ltd.

• Founded in:

  2005-10-18

• Address:

  No. 273-A, Nanhai Avenue, National High-tech Zone, Haikou City

• Tax NO.:

  91460000780701210W

• Registered Funds:

  40 million yuan

• Website:

  Log in to view

• Email:

  Log in to view