Choose two peer posts and reply in a well-developed paragraph (300–350 words) to each peer, integrating an evidence-based resource that is different than the one you used for the initial post.
Respectfully agree and disagree with your peers’ responses and explain your reasoning by including your rationales in your explanation.
Peer 1: Samantha Diagnosis
: Generalized Tonic-Clonic Seizure
- Which of the following should be true regarding your initial Antiepileptic Drugs (AED) regimen?
- Initial combination therapy is warranted due to increased success rates.
- Drugs that are taken two to three times daily are preferred due to a lower risk of seizure if a dose is missed.
- Levetiracetam is the preferred agent for all seizure types and patients.
- The risks of pregnancy must be discussed prior to starting any AED.
In the described scenario, Shaynah’s first suspected seizure event occurred after suffering a head trauma from a softball injury classifying this as a provoked seizure, or one that occurs from an acute condition including head trauma (Karceski, 2022). Shaynah’s first seizure occurred the day following her suspected head trauma event, and her boyfriend reports that Shaynah has suffered from an additional seizure at the 2-month follow-up visit. Suffering from a seizure more than one week after suffering a traumatic head injury is classified as posttraumatic epilepsy (Evans & Schachter, 2022). Shaynah’s head injury should be evaluated with a CT scan and an antiseizure medication should be started (Evans & Schachter, 2022). When considering Shaynah’s unique situation, she is considerably healthy with a history of insulin-dependent diabetes, suspected heartburn, and reported headaches, but she is also looking to have child within the next 1-2 years. The first-line treatment options for women with epilepsy looking to conceive are lamotrigine or levetiracetam with the “most abundant and consistent data for low structural and neurodevelopmental teratogenic risk during pregnancy� (Pennell & McElrath, 2022). Regardless of the antiseizure medication that is started, risks of pregnancy and potential teratogenic effects of medications is a conversation that needs to occur between the provider and Shaynah in this situation.
- Which of the following is the most appropriate initial antiepileptic regimen for this patient?
- Levetiracetam 500 mg PO daily
- Phenytoin 100 mg PO three times daily
- Pregabalin 50 mg PO three times daily
- Clobazam 5 mg PO twice daily
Out of the medication choices provided, Levetiracetam is the most fitting for Shaynah’s situation, however I do not agree with the dosing suggested. For generalized onset seizures, immediate release Levetiracetam should be prescribed initially at 500 mg PO BID and extended release Levetiracetam has an initial prescription recommendation of 1 gram once daily (Lexicomp, n.d.d). Schachter (2022) further supports the initial dosing of 500 mg twice daily. Use of phenytoin in pregnancy can cause congenital malformations including orofacial clefts, growth abnormalities, cardiac defects, as well as bleeding disorders and malignancies (Lexicomp, n.d.e). Pregabalin is only recommended for focal onset seizures and use in pregnancy is limited (Lexicomp, n.d.f). Use of Clobazam is not supported for treating generalized onset seizures is associated with increased risk for fetal malformations, neonate complications including respiratory depression, impaired thermoregulation, low-birth weight, and withdrawal symptoms (Lexicomp, n.d.a).
- The patient fails to respond and has significant side effects to her initial therapy. Her initial therapy is to be discontinued. Which of the following would be the most appropriate replacement?
- Valproic acid 500 mg twice daily
- Lamotrigine 100 mg twice daily
- Lacosamide 100 mg twice daily
- Rufinamide 200 mg twice daily
Valproic acid should not be prescribed as use during pregnancy can have major negative effects on fetal development including neural tube defects, decreased mentation, neurodevelopmental disorders, craniofacial defects, and congenital malformations such as clubfoot, hypospadias, and cardiovascular malformations (Lexicomp, n.d.h). Data on use of Lacosamide in pregnancy is limited but does cross the placenta and is detectable in newborns at birth (Lexicomp, n.d.b). Use of Rufinamide in pregnant animals were observed to have had adverse effects, but this drug has not been evaluated in pregnant patients (Lexicomp, n.d.g). Lamotrigine is approved for treatment of generalized onset seizures and while the drug crosses the placenta, the use of Lamotrigine during pregnancy has not been found to increase the risk for major congenital malformations and can be used during pregnancy with serum monitoring and dose adjustments (Lexicomp, n.d.c). Pregnancy patients may need increases in dosing during pregnancy due to increased clearance of the drug by an uptake of roughly 65% increasing seizure threshold (Schachter, 2022). For Shaynah, Lamotrigine initial dosing should be 25 mg once daily during the first two weeks, then increased to 50 mg/day in 2 doses for weeks 3 and 4, then increase by 50 mg/day every 1-2 weeks with usual dosing being 225-375 mg/day (Schachter, 2022, Lexicomp, n.d.c). So while I agree with the choice of Lamotrigine as a replacement therapy, this dosing does not align with what other resources identify as proper doses, and serum monitoring should be conducted during pregnancy.
- After several different AEDs, the patient ends up on carbamazepine and phenytoin. The carbamazepine serum concentration on week 2 of therapy was 6 mcg/mL. The patient presents after 8 weeks of therapy with increased seizures and she is found to have a serum concentration of 2 mcg/mL. Which of the following is a likely cause?
- Autoinduction of CYP3A4.
- Patient has the HLA-B*1502 subtype.
- The oral contraceptive that she recently started.
- Co-administration with alcohol.
Carbamazepine is metabolized by CYP3A4 enzymes in the liver and carbamazepine 10, 11-epoxide is what can be measured in the blood by serum concentrations (Schachter, 2022). Phenytoin is an interacting drug as a CYP3A4 inducer, and when carbamazepine and phenytoin are taken concurrently the induction of the CYP3A4 enzymes results in increased metabolic rates of Carbamazepine causing decreased serum concentration levels (Woo & Robinson, 2020). This reduction in plasma levels can cause rebound seizure activity (Schachter, 2022).
- Despite the use of oral contraception, the patient becomes pregnant. Her AED regimen consists of valproic acid and lacosamide. What is the most appropriate treatment intervention?
- Discontinue valproic acid and continue lacosamide monotherapy.
- Discontinue lacosamide and continue valproic acid monotherapy.
- Continue combination therapy.
- Discontinue valproic acid and add phenytoin.
As previously mentioned, valproic acid should not be prescribed as use during pregnancy can have major negative effects on fetal development including neural tube defects, decreased mentation, neurodevelopmental disorders, craniofacial defects, and congenital malformations such as clubfoot, hypospadias, and cardiovascular malformations (Lexicomp, n.d.h). Data on use of Lacosamide in pregnancy is limited but does cross the placenta and is detectable in newborns at birth (Lexicomp, n.d.b). Use of phenytoin in pregnancy can cause congenital malformations including orofacial clefts, growth abnormalities, cardiac defects, as well as bleeding disorders and malignancies (Lexicomp, n.d.e). Based on this information, the most appropriate treatment intervention would be to discontinue valproic acid and continue lacosamide monotherapy.
Discussion post: Sara
Generalized Tonic-Clonic Seizures
NU641 – Advanced Pharmacology – week 9
1. Which of the following should be true regarding your initial antiepileptic drug (AED) regimen?
a. Initial combination therapy is warranted due to increased success rates.
b. Drugs that are taken two to three times daily are preferred due to a lower risk of seizure if a dose is missed.
c. Levetiracetam is the preferred agent for all seizure types and patients.
d. The risks of pregnancy must be discussed prior to starting any AED.
There is no single antiepileptic drug (AED) regimen that is perfect for every patient experiencing seizures. Assessing the overall effectiveness of the treatment and how well the patient is able to tolerate side effects of the medication will guide treatment. When initiating an AED regimen, it is very important to discuss pregnancy or the possibility of pregnancy with women of childbearing age as there have been studies noting minor and major fetal malformations from AED exposure in utero (Karceski et al., 2022). Women also need to be educated that AEDs can decrease the effectiveness of hormonal pregnancy contraception making alternative form of contraception necessary. It is noted that about half of the people started on AEDs become seizure free with the first medication prescribed, so monotherapy is appropriate when starting medication (Schachter et al., 2022). Combination therapy is not suggested as it decreases the probability of compliance, is more expensive, and can cause more side effects.
2. Which of the following is the most appropriate initial antiepileptic regimen for this patient?
a. Levetiracetam 500 mg PO daily
b. Phenytoin 100 mg PO three times daily
c. Pregabalin 50 mg PO three times daily
d. Clobazam 5 mg PO twice daily
In Shaynah’s case, the initiation of levetiracetam would be appropriate to treat her tonic-clonic seizure activity. Although phenytoin (Dilantin) is considered a first-line agent for tonic-clonic seizures, it carries a long list of adverse medication interactions including ibuprofen which Shaynah takes daily (Woo & Robinson, 2020). Ibuprofen has been shown to increase plasma hydantoin levels making frequent monitoring of plasma levels imperative. Levetiracetam is a pregnancy category C medication, noting only minor animal fetal malformations. This is important to consider since Shaynah would like to get pregnant in the near future. Phenytoin is a pregnancy category D with known fetal malformations and exposed newborns who lack clotting factors at birth (Schachter et al. 2023). Although levetiracetam 500mg po daily should be changed to bid, loading dosages and titration of daily dosages should be individualized to patient’s overall health and response to medication. Regular follow-up appointments should be scheduled to monitor efficacy of drug and assess side effects. Routine serum monitoring is not seen as necessary with levetiracetam.
3. The patient fails to respond and has significant side effects to her initial therapy. Her initial therapy is to be discontinued. Which of the following would be the most appropriate replacement?
a. Valproic acid 500 mg twice daily
b. Lamotrigine 100 mg twice daily
c. Lacosamide 100 mg twice daily
d. Rufinamide 200 mg twice daily
Factors that contribute to treatment failure of initial AED regimens include female gender, young age, high generalized tonic-clonic seizure burden, and structural abnormalities (Schachter et al., 2022). It is noted that when a replacement medication is initiated, there is a period of weaning off the first medication and increasing of the second to prevent a flurry of seizures during that change. Lacosamide is an anticonvulsant that has been utilized for monotherapy of tonic-clonic seizures in adults with noted success (Schachter et al., 2023). As with most AEDs, decreasing of initial medication while increasing Lacosamide. Valproic acid has a significant side effect of weight gain which could affect Shaynah’s insulin dependence, and Rufinamide has not been approved for tonic-clonic seizures. Lamictal has been approved for adjunctive therapy only when treating tonic-clonic seizures.
4. After several different AEDs, the patient ends up on carbamazepine and phenytoin. The carbamazepine serum concentration on week 2 of therapy was 6 mcg/mL. The patient presents after 8 weeks of therapy with increased seizures and she is found to have a serum concentration of 2 mcg/mL. Which of the following is a likely cause?
a. Autoinduction of CYP3A4.
b. Patient has the HLA-B*1502 subtype.
c. The oral contraceptive that she recently started.
d. Co-administration with alcohol.
When carbamazepine is initiated for seizure treatment, serum levels need to monitored closely to determine therapeutic range. Carbamazepine levels should be initially measured at 3, 6, and 9 months after start of therapy to achieve a level of 4-12mch/mL (Schachter et al., 2023). This is done as carbamazepine can cause autoinduction of CYP3A4, meaning the medication starts producing enzymes responsible for its own metabolism causing the serum concentrations to drop. Due to the decrease in serum concentrations, an increase in carbamazepine would be necessary to achieve an appropriate therapeutic level. Levels should then be monitored every 2-3 months or more frequently if changes in dosages are more frequent or there is a change in combination AED dosages.
5. Despite the use of oral contraception, the patient becomes pregnant. Her AED regimen consists of valproic acid and lacosamide. What is the most appropriate treatment intervention?
a. Discontinue valproic acid and continue lacosamide monotherapy.
b. Discontinue lacosamide and continue valproic acid monotherapy.
c. Continue combination therapy.
d. Discontinue valproic acid and add phenytoin.
Valproic acid has been found to have the highest incidence of fetal major malformations when exposed in utero of all antiseizure medications (Pennell et al., 2022). It can cause neuro tube-like defects as well as multiple malformations and neurodevelopment problems. Valproic acid should be avoided in pregnancy. There is limited information concerning lacosamide in pregnancy; however, animal and preliminary studies have been reassuring. This being said, patients need to be aware there is still a possibility of adverse effects related to AEDs. If Shaynah’s seizures are able to be controlled with lacosamide, adding another medication to the regimen should be avoided. Phenytoin is a pregnancy class D and has been linked to malformations (Pennell et al., 2022). It also has many side effects that could prove to be intolerable in pregnancy. Whenever able, monotherapy is recommended.