Interactions : אינטראקציות

4.5.    Interaction with other medicinal products and other forms of interaction
Contraindicated combinations
+ St. John's Wort
There is a risk of decreased plasma concentrations and reduced efficacy of the antiepileptic.
Inadvisable combinations
+ Lamotrigine
There is a higher risk of serious skin reactions (toxic epidermal necrolysis).
Furthermore, an increase in lamotrigine plasma concentrations may occur (decreased hepatic metabolism by sodium valproate).
If coadministration proves necessary, close clinical monitoring is required.
+ Penems (carbapenems)
There is a risk of seizures due to a rapid decrease in valproic acid plasma concentrations, which may become undetectable.
Co-administration of valproic acid and carbapenems has led to decreases in plasma concentrations of valproic acid of approximately 60 to 100% in around two days. Due to the rapid onset and the extent of the decreased plasma concentrations, simultaneous administration of carbapenems in patients stabilised on valproic acid who cannot be monitored should therefore be avoided (see section 4.4).
Combinations requiring precautions for use
+ Acetazolamide
Increased hyperammonemia with increased risk of encephalopathy may occur.
Regular monitoring of clinical and laboratory parameters is required.
+ Aztreonam
There is a risk of seizures due to a decrease in valproic acid plasma concentrations.
Clinical monitoring, plasma assays and possible dose adjustment of the anticonvulsant are required during treatment with the anti-infective agent and after its discontinuation.
+ Carbamazepine
Increased plasma concentrations of the active metabolite of carbamazepine with signs of overdose may occur. In addition, reduced valproic acid plasma concentrations may occur due to its increased hepatic metabolism by carbamazepine.
Clinical monitoring, plasma assays and dose adjustment of both anticonvulsants are required.
+ Felbamate
Increased serum valproic acid concentrations with a risk of overdose may occur.
Clinical monitoring and monitoring of laboratory parameters and possible valproate dose adjustment are required during treatment with felbamate and after its discontinuation.
+ Estrogen-containing products, including estrogen-containing hormonal contraceptives Estrogens are inducers of the UDP-glucuronosyl transferase (UGT) isoforms involved in valproate glucuronidation and may increase valproate clearance, which in turn is thought to cause a decrease in serum valproate concentrations and to potentially reduce valproate efficacy (see section 4.4). Consider monitoring valproate serum levels.
Conversely, valproate has no enzyme-inducing effect; as a consequence, valproate does not reduce the efficacy of estro-progestative agents in women receiving hormonal contraception.
+ Metamizole
Metamizole may decrease valproate serum levels when co-administered, which may result in potentially decreased valproate clinical efficacy.
Prescribers should monitor clinical response (seizure control or mood control) and consider monitoring valproate serum levels as appropriate.
+ Nimodipine (oral route and, by extrapolation, by injection)
There is a risk of a 50% increase in plasma nimodipine concentrations. Therefore, nimodipine dose reduction is necessary in hypotensive patients.
+ Phenobarbital, and by extrapolation primidone
Increased hyperammonemia with increased risk of encephalopathy may occur.
Regular monitoring of clinical and laboratory parameters is required.
+ Phenytoin, and by extrapolation fosphenytoin
Increased hyperammonemia with increased risk of encephalopathy may occur.
Regular monitoring of clinical and laboratory parameters is required.
+ Propofol
A possible increase in propofol blood levels may occur. When coadministered with valproate, a reduction in propofol dose should be considered.
+ Rifampicin
There is a risk of seizures due to increased hepatic metabolism of valproate by rifampicin.
Clinical monitoring and monitoring of laboratory parameters and possible anticonvulsant dose adjustment are required during treatment with rifampicin and after its discontinuation.
+ Rufinamide
A possible increase in rufinamide concentrations may occur, in particular in children weighing less than 30 kg.
In children weighing less than 30 kg: the total dose of 600 mg/day after dose titration should not be exceeded.
+ Topiramate
Increased hyperammonemia with increased risk of encephalopathy may occur.
Regular monitoring of clinical and laboratory parameters is required.
+ Zidovudine
There is a risk of increased adverse effects of zidovudine, particularly hematological effects, due to decrease in its metabolism by valproic acid.
Regular monitoring of clinical and laboratory parameters is required. A blood count should be performed to test for anemia during the first 2 months of the combination.
+ Zonisamide
Increased hyperammonemia with increased risk of encephalopathy may occur.
Regular monitoring of clinical and laboratory parameters is required.
Other forms of interaction
+ Lithium
Depalept has no effect on serum lithium levels.
+ Risk of liver damage
The concomitant use of salicylates should be avoided in children under 3 years due to the risk of liver toxicity (see section 4.4).
Concomitant use of valproate and other anticonvulsants increases the risk of liver damage, especially in young children (see section 4.4).
Concomitant use with cannabidiol increases the incidence of raised transaminases. In patients of all ages receiving concomitantly cannabidiol at doses of 10 to 25 mg/kg and valproate, clinical trials have reported ALT increases greater than 3 times the upper limit of normal in 19% of patients. Appropriate liver monitoring should be exercised when valproate is used concomitantly with other anticonvulsants with potential hepatotoxicity, including cannabidiol. Dose reductions or therapy cessation should be considered in case of significant anomalies of liver parameters (see section 4.4).