Treatment: antiepileptics (valproate, carbamazepine, oxcarbazepine, lamotrigine, phenytoin, phenobarbital)

Before starting

• Serum β-hCG (girl who has started menstruating, or woman of childbearing potential)if neededValproate must not be started in a woman of childbearing potential without a negative serum pregnancy test (sensitivity of at least 25 mIU/mL); the test is repeated at regular intervals during treatment ^[3].
• FBC with platelets
• PT, aPTT
• AST
• ALT
• Bilirubin
• Serum ammonia (if urea cycle disorder suspected; in children, fasting and after the meal)if neededValproate is contraindicated in urea cycle disorders; if one is suspected, metabolic tests are done before treatment. In a child with unexplained hepatic or digestive history, episodes of lethargy or early family deaths, fasting and post-meal ammonia is requested ^[3].

15 days after starting

• FBC with platelets
• PT, aPTT

Then regularly during the first 6 months

• AST
• ALT
• PT
• Serum β-hCG (girl who has started menstruating, or woman of childbearing potential)if neededTest repeated at regular intervals throughout treatment ^[3].
• Serum lipase (if abdominal pain, nausea, vomiting)if neededPancreatitis, sometimes fatal, at any age and at any duration of treatment; if pancreatic enzymes are raised, stop valproate ^[3].
• Serum ammonia (combination with topiramate, zonisamide, phenobarbital, phenytoin or acetazolamide; ataxia, impaired consciousness, vomiting)if neededThe SmPC reports increased hyperammonaemia, with a risk of encephalopathy, in combination with topiramate, zonisamide, phenobarbital, phenytoin or acetazolamide, and asks for regular clinical and laboratory monitoring; the patient must report any sign of hyperammonaemia (ataxia, altered consciousness, vomiting) ^[3]. An isolated, moderate hyperammonaemia, without liver abnormality, can occur in polytherapy and does not lead to stopping treatment; neurological signs require investigation ^[3].
• Repeat FBC, PT and aPTT before any surgery and in case of haematomas or spontaneous bleeding.

Before starting

• FBC with platelets
• Serum electrolytes (sodium)
• AST
• ALT
• GGT
• Alkaline phosphatase
• Serum β-hCG (woman who could become pregnant)if neededA pregnancy test is done before initiation in women who could become pregnant ^[10].
• HLA-B*15:02 allele testing (Han Chinese, Thai or South-East Asian origin)if neededThe allele is strongly associated with Stevens-Johnson syndrome and Lyell syndrome on carbamazepine in these patients; if present, do not start carbamazepine unless there is no alternative ^[10]. The test is also recommended before oxcarbazepine ^[11]. No dedicated NABM code: not reimbursed in France ^[12]. The SmPC of Tegretol also asks, “as far as possible” and “in some patients”, for testing for the HLA-A*31:01 allele, associated in people of European and Japanese origin with an increased risk of skin reactions (including DRESS) ^[10]; the SmPC of Trileptal, on the contrary, judges the data insufficient to recommend this screening routinely before carbamazepine ^[11]. No dedicated NABM code ^[12].
• TSH (if hypothyroidism on replacement)if neededCarbamazepine can lower thyroid hormones by enzyme induction and require an increase in levothyroxine ^[10].

Once a week during the first month

• AST
• ALT
• GGT
• Alkaline phosphatase

About 2 weeks after starting, then every month for 3 months (if risk of hyponatraemia)

• Serum electrolytes (sodium)if neededOlder person, renal failure with low serum sodium, or concomitant hyponatraemia-inducing treatment (diuretic, drug promoting inappropriate ADH secretion) ^[10].

Once a month for the first 5 months, then 2 to 4 times a year

• FBC with platelets

During treatment, depending on the context

• 25-hydroxyvitamin D (vitamin D supplementation, or signs of osteomalacia)if neededInteraction requiring precautions for use: carbamazepine lowers vitamin D concentrations; the SmPC recommends measuring vitamin D and supplementing if necessary ^[10]. Bone metabolism disorders (lower serum calcium and 25-hydroxyvitamin D, osteomalacia, osteoporosis) are described, very rarely ^[10]. Covered: the NABM covers the tests recommended by an SmPC ^[12].

Before starting (if risk of hyponatraemia)

• Serum electrolytes (sodium)if neededRenal failure with low serum sodium, SIADH, concomitant hyponatraemia-inducing treatment (diuretic, desmopressin) or NSAID, older person ^[11].
• HLA-B*15:02 allele testing (Han Chinese, Thai or Asian origin)if neededPossible risk of Stevens-Johnson or Lyell syndrome in carriers, by analogy with carbamazepine; screening recommended when possible ^[11]. Not reimbursed in France ^[12].

About 2 weeks after starting, then every month for 3 months (if risk of hyponatraemia)

• Serum electrolytes (sodium)if neededSame at-risk population; same frequency if a hyponatraemia-inducing treatment is added later ^[11].

No routine laboratory tests: measure levels only in particular situations

• Lamotrigine (blood level, in the morning before the dose)if neededStarting or stopping a combined oestrogen-progestogen contraceptive, pregnancy, adding or withdrawing an interacting drug (valproate, inducers), seizures resuming or suspected toxicity ^[16,17].

Trough sample, in the morning before the dose (about 12 hours after the last dose)

• Valproic acid (serum level)if neededUncontrolled seizures or suspected adverse effects; usual range 40 to 100 mg/L ^[3]. Use as a mood stabiliser: two levels in range in the acute phase, then every 3 to 6 months ^[4]. Oestrogens, including combined oestrogen-progestogen contraceptives, can increase valproate clearance: consider a level ^[3].
• Carbamazepine (serum level)if neededNeurological signs of overdose or polytherapy; usual range 4 to 12 µg/mL ^[10]. Use as a mood stabiliser: every 6 to 12 months ^[4].
• Phenytoin (serum level)if neededAt the first sign of toxicity; at each dose adjustment, because its pharmacokinetics are non-linear; during and after folate supplementation ^[17,19]. Effective concentrations according to the SmPC: generally 5 to 12 mg/L in adults and 10 to 20 mg/L in children; steady state reached only after 8 to 20 days ^[19].
• Phenobarbital (serum level)if neededInteraction, including folate supplementation ^[20]; suspected toxicity or non-adherence ^[17]. Sample preferably in the morning; usual range 15 to 30 mg/L (65 to 130 µmol/L) in adults, about 20 mg/L (85 µmol/L) in children ^[20].