Absenor®: composition and dosage form
One tablet contains 300 mg or 500 mg of sodium valproate. This is a prolonged-release form, and the point of it is to prevent peak concentrations of valproic acid from arising: the substance is released evenly and stays in the blood at a more stable level through the day.
Hence the rule for taking it: the tablet is swallowed whole with plenty of liquid, and it must not be chewed or crushed — a broken coating cancels the whole prolonged release. If irritation of the digestive tract appears at the start of treatment or during it, the tablet is taken with or after a meal. Two small points from the product information: the 300 mg tablet contains 42 mg of sodium and the 500 mg tablet 69 mg, which matters on a sodium-controlled diet.
How Absenor® works
Sodium valproate is an antiepileptic medicine and, chemically, a branched fatty acid that resembles no other anticonvulsant substance in structure. Its mechanism of action is not fully understood. Preclinical studies indicate that valproate raises the concentration of the inhibitory neurotransmitter — gamma-aminobutyric acid — in the synaptic cleft, affects the excitatory neurotransmitters, and may act directly on the sodium and potassium channels in neuronal membranes.
That incomplete knowledge of the mechanism has a practical consequence which the product information states plainly: no strict relationship has been established between the daily dose, the concentration of the medicine in serum, and the therapeutic effect. The dose is therefore fitted to the clinical result, not to the test.
Indications
The main field is epilepsy. The medicine is prescribed for primarily generalised seizures: typical and atypical absences, myoclonic and tonic-clonic seizures, mixed forms of absences with tonic-clonic seizures, and atonic seizures. It is used as well in other forms of epilepsy that do not respond adequately to other medicines — in simple and complex partial seizures and in secondarily generalised ones, particularly akinetic and atonic.
The second indication is the manic phase of bipolar affective disorder, and with a caveat: treating manic episodes with valproate is considered when lithium is contraindicated or poorly tolerated. Continuing the treatment is possible in those patients who obtained a clinical response in the acute phase of mania.
Method of administration and dosage
In epilepsy the dose is set and reviewed by a specialist, and the aim is stated as freedom from seizures on the smallest dose. Monotherapy is usually begun with 5-10 mg of sodium valproate per kilogram of body weight, and the daily dose is raised gradually, every 4-7 days by about 5 mg/kg, until the seizures come under control. The average maintenance daily dose in adults and older people is about 20 mg/kg.
In manic episodes the schedule is different and faster. The recommended starting daily dose is 750 mg. The prolonged-release form is given once or twice a day, and the dose is raised as quickly as possible to the lowest concentration giving the desired clinical effect; the average daily dose usually falls between 1000 and 2000 mg. Patients receiving more than 45 mg/kg a day must remain under close observation. Children and adolescents under 18 are not prescribed the medicine for mania: its safety and efficacy have not been established in that group.
Contraindications
The list is short but dense: hypersensitivity to the active substance or to any excipient; acute and chronic hepatitis; severe hepatic failure, particularly drug-induced in the personal or family history; severe pancreatic insufficiency; porphyria; a tendency to bleed; urea cycle disorders.
On a line of its own stand mitochondrial disorders caused by mutations of the nuclear POLG gene, which encodes mitochondrial polymerase gamma — Alpers-Huttenlocher syndrome, for example — along with children under two years of age in whom such disorders are suspected. The reason is that it is precisely in these patients that valproate-induced acute liver failure and deaths from liver damage have been described more often.
Special warnings and precautions
The first restriction is placed at the very beginning of the section and sounds categorical: the medicine should not be used in girls, in women of childbearing potential, or in pregnant women, unless other methods of treatment are ineffective or not tolerated. Women of childbearing potential are obliged to use reliable contraception throughout treatment.
| When | What is checked | What a deviation means |
| Before treatment begins | a detailed personal and family history, indicators of liver and pancreatic function, investigation for metabolic disorders and coagulopathies | a liver or pancreatic disease or a clotting disorder found here most often means the medicine is not prescribed at all |
| At 4 weeks | full blood count with differential and platelet count, coagulation parameters, transaminases, alkaline phosphatase, bilirubin, amylase | of the liver tests, the ones that matter most are those reflecting protein synthesis, above all prothrombin; an isolated rise in enzymes without symptoms is not yet a verdict |
| Monthly for the first 6 months | clinical condition and the same laboratory parameters | it is to this period, most often between the 2nd and 12th weeks, that the majority of cases of liver damage belong |
No test, however, replaces watching how the patient feels, because abnormalities in the blood are not present in every case. Suddenly appearing weakness, drowsiness, confusion, loss of appetite, abdominal pain, vomiting, aversion to familiar food or to the medicine itself, a tendency to bleed, oedema and the return of seizures on properly adjusted treatment — all of this can precede jaundice and calls for seeing a doctor at once. Separately, the product information warns of suicidal thoughts and behaviour in patients taking antiepileptic medicines, and of a considerable gain in body weight, which itself becomes a risk factor for polycystic ovary syndrome.
Interaction with other medicines
The interactions here run both ways, and it is easier to take them by direction. The concentration of valproate itself is lowered by carbamazepine, phenytoin, phenobarbital and primidone, and also by rifampicin, which raises its clearance, and by mefloquine, with which the combination is not recommended. The carbapenems stand apart: they reduce the concentration of valproic acid by 60-100% over roughly two days, and a fall that fast makes fitting a dose simply impossible, so the combination is avoided.
Valproate itself inhibits the metabolism of a whole series of medicines. The most important combination is with lamotrigine: valproate lengthens its half-life and increases its toxicity, so concurrent use is not recommended and, where necessary, the lamotrigine dose is reduced; the risk of severe skin reactions also rises, particularly in children and particularly in the first six months of taking them together. Phenytoin is displaced by valproate from its protein binding, so it is the free fraction that must be measured. The metabolism of phenobarbital and primidone it inhibits, and if sedation or other signs of barbiturate poisoning appear their dose is cut at once — the first 15 days of the combination call for particularly careful observation.
Pregnancy and breastfeeding
This is the most important section of valproate's product information and, unlike that of many medicines, it rests not on cautious wording but on figures. In women planning a pregnancy the treatment is changed, as far as possible, to an alternative before conception. Stopping it on one's own, however, is not allowed: the decision is taken by a doctor specialising in epilepsy or bipolar disorder, because tonic-clonic seizures and status epilepticus with hypoxia in the mother are in themselves lethally dangerous both to her and to the child.
- congenital malformations have been described in 10.73% of the children of women with epilepsy who received valproate monotherapy during pregnancy (confidence interval 8.16-13.29) — against roughly 2-3% in the general population;
- the risk depends on the dose, but no threshold dose below which it disappears could be established; polytherapy including valproate is more dangerous than monotherapy;
- most often these are neural tube defects, facial dysmorphism, cleft lip and palate, craniostenosis, malformations of the heart, kidneys and genitourinary system, and limb defects;
- in 30-40% of preschool children exposed to valproate in fetal life, early developmental delay was found: a later start to speaking and walking, weaker language ability and problems with memory;
- the intelligence quotient measured at six years was on average 7 to 10 points lower than in children exposed to other antiepileptic medicines;
- the risk of autism spectrum disorders is about threefold higher and that of childhood autism about fivefold; there is data too on a more frequent attention deficit hyperactivity disorder;
- in newborns there have been reports of haemorrhagic syndrome with thrombocytopenia and a fall in fibrinogen, hypoglycaemia where the medicine was taken in the third trimester, hypothyroidism, and withdrawal symptoms — irritability, tremor, disturbed muscle tone, convulsions and feeding difficulties.
If, after weighing benefit against risk, treatment is nonetheless continued, the smallest effective dose is used, split through the day into several small administrations, and the prolonged-release form is preferred so as to avoid high plasma concentrations. Taking folates before pregnancy lowers the neural tube defect risk common to all pregnancies, but there is no evidence that it prevents valproate-related malformations specifically. Valproate passes into breast milk in an amount between 1 and 10% of the concentration in the mother's serum, and blood disorders have been described in breastfed children, so the question of stopping feeding or stopping treatment is settled by weighing the benefit of each.
Adverse effects
Very common are a rise in blood ammonia, nausea and tremor. Common reactions include anaemia, thrombocytopenia or leucopenia — these often pass in the course of treatment and always disappear completely after withdrawal — weight gain, confusion, hallucinations, aggression, agitation and impaired concentration observed mainly in children, extrapyramidal disorders, drowsiness, paraesthesia, convulsions, memory disturbance, headache, and also dose-dependent severe liver damage, hypersensitivity, transient hair loss and painful menstruation.
Rarer but graver is the second half of the list. Damage to the pancreas sometimes ends in death. Stupor and lethargy may progress to a transient coma and encephalopathy — more often on combination treatment, particularly with phenobarbital and topiramate, or after a rapid dose increase — and resolve when the dose is reduced or the medicine withdrawn. Severe skin reactions have also been described: Stevens-Johnson syndrome, toxic epidermal necrolysis and drug rash with eosinophilia, and with prolonged use a fall in bone mineral density going as far as pathological fractures.
Overdose
A moderate overdose shows itself as drowsiness, lethargy, nausea, vomiting, dizziness and a fast heartbeat. A substantial one looks different: coma, respiratory depression, metabolic acidosis, a fall in platelet and leucocyte counts, a fall in blood pressure, convulsions and hypoglycaemia. Fatal outcomes have been described.
There is no specific antidote, so treatment is guided by the symptoms: activated charcoal is given repeatedly, vital functions are monitored, and in substantial overdose haemodialysis and forced diuresis have been used. One important practical detail: after an overdose absorption usually slows, so charcoal or gastric lavage are of use even 6-12 hours after the medicine was taken.
How to get a prescription for Absenor® online
Valproate carries the strictest restriction by sex and age of any antiepileptic: girls, adolescent girls and women of childbearing potential are not prescribed it until other options have been exhausted, and prescribing it requires reliable contraception and an understanding of the risk figures. The second thing that decides the doctor's answer is the state of the liver and pancreas, because the first six months of treatment run to a timetable of tests. On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with the diagnosis and your current regimen: which form of epilepsy or which episode of bipolar disorder, which medicines you take now and at what dose, whether valproate has already been used and in what form. Women must state their age, their method of contraception, their plans regarding pregnancy, and whether a switch to another treatment has been discussed. Give your latest test results with their dates: liver function tests, amylase and a full blood count with platelets. Report liver and pancreatic disease, including in relatives, and any tendency to bleed. List the medicines: lamotrigine, phenytoin, phenobarbital, carbamazepine, antibiotics of the carbapenem group, rifampicin — each of them changes either the dose or the very possibility of treatment.
