Out of these, Primidone poisoning was much less common than phenobarbital poisoning. Twenty-seven of those adult cases were reported to the Dutch National Poison Control Center. Out of these, one person taking it with phenytoin and phenobarbital died, twelve became drowsy and four were comatose.Treatments for primidone overdose have included hemoperfusion with forced diuresis, a combination of bemegride and amiphenazole; and a combination of bemegride, spironolactone, caffeine, pentylenetetrazol, strophanthin, penicillin and streptomycin.In the three adults who are reported to have succumbed, the doses were 20–30 g. However, two adult survivors ingested 30 g 25 g, and 22.5 g. One woman experienced symptoms of primidone intoxication after ingesting 750 mg of her roommates primidone. Interactions
Taking primidone with monoamine oxidase inhibitors (MAOIs) such as isocarboxazid (Marplan), phenelzine (Nardil), procarbazine (Matulane), selegiline (Eldepryl), tranylcypromine (Parnate) or within two weeks of stopping any one of them may potentiate the effects of primidone or change ones seizure patterns. Isoniazid, an antitubercular agent with MAOI properties, has been known to strongly inhibit the metabolism of primidone.Like many anticonvulsants, primidone interacts with other anticonvulsants. Clobazam decreases clearance of primidone,Mesuximide increases plasma levels of phenobarbital in primidone users, both primidone and phenobarbital accelerate the metabolism of carbamazepine via CYP3A4, and lamotrigines apparent clearance is increased by primidone. In addition to being an inducer of CYP3A4, it is also an inducer of CYP1A2, which causes it to interact with substrates such as fluvoxamine, clozapine, olanzapine, and tricyclic antidepressants.
In addition to all of the above, primidone can cause arthralgia.Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, and megaloblastic anemia are rarely associated with the use of primidone. Megaloblastic anemia is actually a group of related disorders with different causes that share morphological characteristics—enlarged red blood cells with abnormally high nuclear-cytoplasmic ratios resulting from delayed maturation of nuclei combined with normal maturation of cytoplasm, into abnormal megakaryocytes and sometimes hypersegmented neutrophils; regardless of etiology, all of the megaloblastic anemias involve impaired DNA replication. The anticonvulsant users who get this also tend to eat monotonous diets devoid of fruits and vegetables.This antagonistic effect is not due to the inhibition of dihydrofolate reductase, the enzyme responsible for the reduction of dihydrofolic acid to tetrahydrofolic acid, but rather to defective folate metabolism.In addition to increasing the risk of megaloblastic anemia, primidone, like other older anticonvulsants also increases the risk of neural tube defects, and like other enzyme-inducing anticonvulsants, it increases the likelihood of cardiovascular defects, and cleft lip without cleft palate. Epileptic women are generally advised to take folic acid, but there is conflicting evidence regarding the effectiveness of vitamin supplementation in the prevention of such defects.Additionally, a coagulation defect resembling Vitamin K deficiency has been observed in newborns of mothers taking primidone.