Valproic acid

Valproic acid

1 Drinking alcohol can increase the sedative effect. 2 When general anesthetics or central nervous system depressants are used in combination with valproic acid, the clinical effect of the former may be more obvious. 3 When used in combination with anticoagulants such as warfarin or heparin, as well as thrombolytics, it may increase the effect of anticoagulants; valproic acid can cause hypoprothrombinemia and inhibit platelet aggregation. When anticoagulants or thrombolytics are given, the risk of bleeding increases. 4 When used in combination with aspirin or dipyridamole, it can prolong bleeding time due to reduced platelet aggregation. 5 When used in combination with phenobarbital drugs, the latter's metabolism slows down and the blood drug concentration increases, thereby increasing the sedative effect and causing drowsiness. 6 When used in combination with primidone, it can also cause an increase in blood drug concentration and lead to poisoning. If necessary, the dosage of primidone needs to be reduced. 7 When used in combination with clonazepam to prevent and treat absence seizures, there have been reports of a few cases where it has induced absence states. 8 When used in combination with phenytoin, the competition with protein binding may change the blood concentration of both drugs. Since the concentration of phenytoin varies greatly, it needs to be measured frequently, but whether the dosage needs to be adjusted depends on the clinical situation and blood concentration. 9 When used in combination with carbamazepine, the induction of liver enzymes can accelerate drug metabolism, which can reduce the blood concentration and half-life of both drugs. Therefore, it is necessary to monitor the blood concentration to determine whether the dosage needs to be adjusted. 10 When used in combination with drugs that are toxic to the liver, there is a potential risk of liver poisoning. Long-term use in patients with a history of liver disease requires regular liver function checks. 11 When used in combination with haloperidol, loxapine, maprotiline, monoamine oxidase inhibitors, phenothiazines, thioxanthenes and tricyclic antidepressants, it can increase the inhibition of the central nervous system, reduce the convulsion threshold and the effect of valproic acid, and the dosage needs to be adjusted in time to control seizures. Salicylic acid can inhibit the metabolism of valproate, prolonging its half-life, and the combination of the two can affect blood coagulation and platelet function. Salicylic acid cannot be used in combination with valproate in children to avoid Reye syndrome. Naproxen interferes with the protein binding of valproate. The combination of erythromycin and valproate is prone to toxic symptoms of valproate. Carbamazepine, phenytoin, and phenobarbital can reduce serum valproate concentrations; and valproate inhibits phenobarbital metabolism, which increases phenobarbital blood concentrations. The combination of valproate with clonazepam, nitrazepam, etc. can aggravate drowsiness. Taking the antimalarial drug mefloquine can greatly reduce the blood concentration of valproate. The bioavailability of valproate preparations is increased after using aluminum hydroxide or magnesium hydroxide, and other antacids are not effective. Cimetidine prolongs the half-life of valproate, while ranitidine does not have this effect. Avoid using it in combination with aspirin and warfarin.

Valproic acid.

1 Drinking alcohol can increase the sedative effect. 2 When general anesthetics or central nervous system depressants are used in combination with valproic acid, the clinical effect of the former may be more obvious. 3 When used in combination with anticoagulants such as warfarin or heparin, as well as thrombolytics, it may increase the effect of anticoagulants; valproic acid can cause hypoprothrombinemia and inhibit platelet aggregation. When anticoagulants or thrombolytics are given, the risk of bleeding increases. 4 When used in combination with aspirin or dipyridamole, it can prolong bleeding time due to reduced platelet aggregation. 5 When used in combination with phenobarbital drugs, the latter's metabolism slows down and the blood drug concentration increases, thereby increasing the sedative effect and causing drowsiness. 6 When used in combination with primidone, it can also cause an increase in blood drug concentration and lead to poisoning. If necessary, the dosage of primidone needs to be reduced. 7 When used in combination with clonazepam to prevent and treat absence seizures, there have been reports of a few cases where it has induced absence states. 8 When used in combination with phenytoin, the competition with protein binding may change the blood concentration of both drugs. Since the concentration of phenytoin varies greatly, it needs to be measured frequently, but whether the dosage needs to be adjusted depends on the clinical situation and blood concentration. 9 When used in combination with carbamazepine, the induction of liver enzymes can accelerate drug metabolism, which can reduce the blood concentration and half-life of both drugs. Therefore, it is necessary to monitor the blood concentration to determine whether the dosage needs to be adjusted. 10 When used in combination with drugs that are toxic to the liver, there is a potential risk of liver poisoning. Long-term use in patients with a history of liver disease requires regular liver function checks. 11 When used in combination with haloperidol, loxapine, maprotiline, monoamine oxidase inhibitors, phenothiazines, thioxanthenes and tricyclic antidepressants, it can increase the inhibition of the central nervous system, reduce the convulsion threshold and the effect of valproic acid, and the dosage needs to be adjusted in time to control seizures. Salicylic acid can inhibit the metabolism of valproate, prolonging its half-life, and the combination of the two can affect blood coagulation and platelet function. Salicylic acid cannot be used in combination with valproate in children to avoid Reye syndrome. Naproxen interferes with the protein binding of valproate. The combination of erythromycin and valproate is prone to toxic symptoms of valproate. Carbamazepine, phenytoin, and phenobarbital can reduce serum valproate concentrations; and valproate inhibits phenobarbital metabolism, which increases phenobarbital blood concentrations. The combination of valproate with clonazepam, nitrazepam, etc. can aggravate drowsiness. Taking the antimalarial drug mefloquine can greatly reduce the blood concentration of valproate. The bioavailability of valproate preparations is increased after using aluminum hydroxide or magnesium hydroxide, and other antacids are not effective. Cimetidine prolongs the half-life of valproate, while ranitidine does not have this effect. Avoid using it in combination with aspirin and warfarin.

This product is a compound preparation, and its components are: each tablet contains 0.333g sodium valproate and 0.145g valproic acid (equivalent to 0.5g sodium valproate).

Taking drugs that induce seizures or lower the seizure threshold at the same time as this product should be carefully considered. Depending on the severity of the potential risk, it may be determined not to use or be prohibited. This type of drug mainly includes most antidepressants (imipramine, SSRI), tranquilizers (phenothiazines and phenoxybenzene drugs), mequinine (see the following chapters), bucycline, tramadol, etc. Prohibited combined use: 1. Combined use with mequinine: When taken in combination with epilepsy patients, mequinine may increase valproic acid metabolism and its own seizure induction effect may cause them to have the risk of epileptic seizures. 2. Combined use with St. John's wort: There is a risk of reduced blood drug concentration and reduced anticonvulsant efficacy. Combined use that requires attention: 1. Combined use with aztreonam, imipenem, and meropenem: There is a risk of spasmodic reactions caused by reduced valproic acid blood drug concentration. During the treatment with anti-infective drugs, clinical monitoring, blood drug concentration measurement, and timely adjustment of the dose of anticonvulsant drugs should be carried out, and monitoring is still required after discontinuation of the drug. 2. Carbamazepine: It can increase the blood concentration of active metabolites of carbamazepine, leading to drug overdose. At the same time, due to the induction of liver metabolism by carbamazepine, the blood concentration of valproate can be reduced. Therefore, clinical drug monitoring is recommended to measure the blood concentration of the two anticonvulsant drugs and adjust their doses: 3. Lamotrigine: The risk of severe skin reactions (Lyell's syndrome) is increased. Valproate can increase the blood concentration of lamotrigine by inhibiting its liver metabolism. If it must be taken together, it should be closely monitored in the clinic. 4. Felbamate: It can increase the blood concentration of valproate, resulting in the risk of drug overdose. During the treatment with felbamate, clinical and biochemical indicators should be monitored and the dose of valproate should be adjusted. The above observation measures should still be taken after discontinuation of the drug. 5. Phenobarbital, primidone: Due to the inhibitory effect of valproate on liver metabolism, the blood concentration of phenobarbital or primidone can be increased, resulting in drug overdose, which is more common in children. At the same time, the blood concentration of valproate can be reduced due to the induction of liver metabolism by phenobarbital or primidone. Clinical monitoring should be carried out within the first 15 days of combined treatment, and the dose of phenobarbital or primidone should be reduced promptly when any symptoms of sedation occur. In particular, the blood concentration of the two anticonvulsant drugs should be monitored. 6. Phenytoin (and by extension, phosphophenytoin): It can cause changes in the blood concentration of phenytoin. At the same time, there is a risk of reduced blood concentration of valproate due to the induction of liver metabolism by phenytoin. Clinical monitoring and blood concentration measurement should be carried out, and the doses of the two anticonvulsant drugs should be adjusted appropriately. 7. Topiramate: There is a risk of hyperammonemia or encephalopathy, which is usually caused by taking valproate at the same time as topiramate. Clinical monitoring and laboratory monitoring should be increased in the early stage of treatment, and signs of this reaction should be noted. 8. Cimetidine and erythromycin: Taking them at the same time may increase the concentration of valproate in the serum. 9. Acetylsalicylic acid: Infants and young children with temperature and sexual dysfunction should not take medicines containing valproic acid and acetylsalicylic acid at the same time. Adolescents with temperature and sexual dysfunction can only take it under the guidance of a doctor. 10. Benzodiazepines, barbiturates and tranquilizers, monoamine oxidase inhibitors and antidepressants: When used in combination, valproic acid can increase the central inhibitory effect of these drugs. Patients should be closely monitored when the above drugs are used in combination. The dosage of the drugs should be adjusted if necessary. 11. Zidovudine: Valproic acid can increase the serum drug concentration of zidovudine, which may lead to increased zidovudine toxicity. Anticoagulants and antiplatelet aggregation drugs: Taking them at the same time with valproic acid-containing drugs may increase the tendency to bleed. Therefore, it is recommended to monitor the coagulation status regularly during the combined use. 12. Diazepam: The results of studies in healthy subjects showed that valproic acid can displace diazepam from its plasma protein binding site and inhibit its metabolism. The plasma concentration of free diazepam in the body may increase, and the plasma clearance and distribution volume of free diazepam may decrease (by 25% and 20%, respectively). However, the half-life remains unchanged. The results of studies in healthy subjects showed that the plasma concentration of lorazepam can be reduced by up to 40% when valproate and lorazepam are taken simultaneously. In children, the level of phenytoin in serum may increase after taking clonazepam and valproic acid at the same time. 13. Nimodipine (administered by oral and intravenous routes): Due to the inhibitory effect of valproic acid on metabolism, the blood concentration of nimodipine may increase, which promotes the hypotensive response of nimodipine. Rifampicin may reduce the blood concentration of valproate, resulting in reduced efficacy. Therefore, when used in combination with rifampicin, it is necessary to adjust the dosage of valproate. Other forms of interaction: With oral contraceptives: Since valproic acid has no enzyme inducing activity, it will not reduce the effect of hormonal contraceptives taken by women on estrogen-progestin.