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Epilepsy > Medication > Flashcards

Medication Flashcards

1
Q

In which type of epilepsy is Sodium Valproate indicated?

A

First line monotherapy:
Generalised tonic-clonic seizures
Myoclonic seizures
Tonic or Atonic seizures
Idiopathic generalised epilepsies
Dravet’s syndrome
Lennox-Gastaut syndrome

Second line:
Absence seizures

Add on:
Focal seizures

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2
Q

Aside from epilepsy what are some of the other indications of Sodium Valproate?

A

Migraine prophylaxis
Mania in bipolar disorder

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3
Q

What formulations and brands of Sodium Valproate are available? Can you switch?

A

Formulations:
Oral tablet
Modified release tablet
Gastro-resistant tablet
Modified release capsule
Modified release granules
Oral solution
Solution for injection
Powder and solvent for injection

Brands:
Sodium valproate
Epilim chronosphere
Epilim chrono
Episenta capsules
Episenta granules
Epival
Dyszantil

Sodium Valproate is within Category 2, ideally the patient should be maintained on the same brand based on clinical and non-clinical factors. However if the brand needs to be switched a consultation with the patient should be done first with respect to clinical judgement such as previous history and seizure frequency.

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4
Q

What are the main side effects associated with Sodium Valproate?

A

Nausea
Weight gain
Polycystic ovary syndrome
Transient elevation of LFTs
Blood dyscrasias
Alopecia (hair regrowth may be curly)
Liver toxicity
Pancreatitis

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5
Q

What is the monitoring required for Sodium Valproate therapy?

A

Therapeutic monitoring:
Plasma-valproate concentrations are not a useful index of efficacy, therefore routine monitoring is unhelpful

Before initiation:
LFTs and FBC (screen for any underlying blood dyscrasias and then monitor closely)

During the first 6 months:
LFTs (including prothrombin time) monitor closely until returned to normal. Discontinue if abnormally prolonged prothrombin time especially if other abnormalities are present

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6
Q

What are the key counselling points associated with Sodium Valproate therapy?

A

Encourage patient self-monitoring and self-reported side effects indicating:

Liver disorders: Jaundice, Abdominal pain, Sudden onset of tiredness, nausea and vomiting, Anorexia, Swelling

Pancreatitis: Nausea and vomiting, Acute abdominal pain

Blood dyscrasias: Bruising, bleeding, sore throat

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7
Q

What are the main pharmacokinetic parameters associated with Sodium Valproate?

A

Sodium valproate has the capability to cross the placenta, therefore teratogenic
Undergoes hepatic metabolism
Half life of 8-20 hours, noticeably shorter in children however
CYP inhibitor of CYP2C9

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8
Q

Are there any key interactions associated with Sodium Valproate?

A

Other drugs increasing the risk of hyponatremia
Other drugs also increasing risk of hepatoxicity

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9
Q

Are formulations of Sodium Valproate bioequivalent?

A

Sodium valproate formulations are interchangeable with other sodium valproate immediate-release, modified-release or liquid formulations. The total daily dose should remain the same. They are bioequivalent.

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10
Q

In which type of epilepsy is Carbamazepine indicated?

A

2nd line treatment:
Focal seizures (monotherapy)
Other types including benign epilepsy with centrotemporal spike

Add on:
Focal seizures

Supposedly in generalised tonic-clonic (not present in NICE guidelines)

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11
Q

Aside from epilepsy what are some of the other indications of Carbamazepine?

A

Prophylaxis in bipolar, unresponsive to Lithium
Trigeminal neuralgia
Adjunct in acute alcohol withdrawal (unlicensed)
Diabetic neuropathy (unlicensed)

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12
Q

What formulations and brands of Carbamazepine are available? Can you switch?

A

Brands:
Carbamazepine (generic)
Carbagen
Tegretol

Formulation:
Oral tablet
Modified release tablet
Oral suspension
Oral solution
Suppository

Carbamazepine is a Category 1 and therefore patient’s should be maintained on a specific brand as there are clinically relevant differences between brands. Increasing the potential for adverse effects and risk of loss of seizure control.

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13
Q

What are the main side effects associated with Carbamazepine?

A

Drowsiness
Dry mouth
Nausea
Vision disturbances (can be dose limiting)
Blood disorders - leukopenia, eosinophilia, thrombocytopenia
Hyponatremia
Skin disorders

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14
Q

What is the monitoring required for Carbamazepine therapy?

A

Pre-screening:
If Han Chinese or Thai origin screen for HLA-B* 1502 allele due to increased risk of Steven Johnson syndrome associated with the presence of this allele.

Therapeutic monitoring:
Plasma concentration for optimum response 4–12 mg/litre (20–50 micromol/litre) measured after 1–2 weeks

Ongoing monitoring:
Manufacturer recommends FBC, Renal and LFTs

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15
Q

What are the key counselling points associated with Carbamazepine therapy?

A

Encourage patient self-monitoring and self-reported side effects indicating:

Liver disorders: Jaundice, Abdominal pain, Sudden onset of tiredness, nausea and vomiting, Anorexia, Swelling

Skin disorders: including Steven-Johnson syndrome symptoms include ulcers of the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). Rashes are often preceded by influenza-like symptoms fever, headache, body ache (flu-like symptoms) and are most likely to occur within the first few months of treatment.

Blood dyscrasias: Bruising, bleeding, sore throat

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16
Q

What are the main pharmacokinetic parameters associated with Carbamazepine?

A

Carbamazepine is a potent CYP450 inducer including CYP3A4 and CYP2B6.
Other CYP inducers/inhibitors affect the clearance rate of Carbamazepine
After continued administration auto-induces its own metabolism altering the half life

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17
Q

Are there any key interactions associated with Carbamazepine?

A

Other CYP inducers/inhibitors
Drugs metabolised by CYP 450 (decreasing exposure)
Other drugs causing hyponatremia
Also interacts with other AEDs

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18
Q

Are formulations of Carbamazepine bioequivalent?

A

Oral formulations are not bioequivalent and therefore correct conversion between formulations need to be calculated.

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19
Q

What is Oxcarbazepine?

A

It is a pro-drug of Carbamazepine converted in the liver to its active metabolite

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20
Q

When is Oxcarbazepine indicated for epilepsy?

A

It is used as second line monotherapy or as first line add on in focal seizures.

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21
Q

Compare the notable pharmacokinetic parameters between Oxcarbazepine and Carbamazepine.

A

Whereas Carbamazepine is a potent CYP 450 inducer, Oxcarbazepine is only a weak CYP inducer of CYP 3A4 and CYP 3A5

However Oxcarbazepine is also a weak CYP 2C19 inhibitor.
Unlike Carbamazepine, Oxcarbazepine does not induce its own metabolism (auto-inducer) and therefore half-life is not affected by continuation of therapy.

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22
Q

If a patient has a sensitivity to Carbamazepine, what is the likelihood they will also have a sensitivity to Oxcarbazepine?

A

In those that are hypersensitive to Carbamazepine, 25-30% will also have hypersensivity to Oxcarbazepine.

Oxcarbazepine is also associated with Antiepileptic hypersensitivity syndrome

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23
Q

Compare the clinical profile of Oxcarbazepine to that of Carbamazepine.

A

Oxcarbazepine is only available in two formulations: oral tablets and suspension.

The side effect profile of Oxcarbazepine is similar to that of Carbamazepine, encourage patients to self monitor blood, liver and skin disorders.

Monitoring requirements also include:
Monitor plasma-sodium concentration in patients at risk of hyponatraemia.
Monitor body-weight in patients with heart failure

Whilst Carbamazepine is Category 1, Oxcarbazepine is Category 2 medication and therefore ideally the patient should be maintained on the same brand based on clinical and non-clinical factors.
However if the brand needs to be switched a consultation with the patient should be done first with respect to clinical judgement such as previous history and seizure frequency.

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24
Q

What is Eslicarbazepine?

A

Similar to oxcarbazepine, Eslicarbazepine is a derivative of Carbamazepine in which it lacks the toxic epoxide functionality.

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25
Q

When is Eslicarbazepine indicated in epilepsy?

A
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26
Q

State the notable pharmacokinetic parameters of Eslicarbazepine.

A

It is a weak inhibitor and inducer of certain CYP enzymes
However does not auto-induce its own metabolism, affecting its half-life after cumulative doses
Has a long half life so only once daily dosing is required

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27
Q

Does Eslicarbazepine also a risk of cross-sensitivity associated with Carbamazepine?

A

Yes there is also a risk of anti-epileptic hypersensivity syndrome.

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28
Q

Describe the clinical profile of Eslicarbazepine.

A

Eslicarbazepine has a similar side effect profile to that of Oxcarbazepine, however it can also cause PR interval prolongation and is C/I in second or third degree AV block.
Monitoring should also include plasma-sodium concentration and discontinuation should occur if hyponatremia is present.
Only available in oral tablets and suspension.
Again like Oxcarbazepine is a Category 2 medication, so ideally should be maintained on the same brand taking into consideration clinical and non-clinical considerations.

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29
Q

In which type of epilepsy is Ethosuximide indicated?

A

First line add on treatment:
Absent seizures including childhood absence seizures

Third line:
Myoclonic-atonic seizures

Also licensed for myoclonic seizures

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30
Q

What formulations and brands of Ethosuximide are available? Can you switch?

A

Formulation:
Oral capsules
Oral solution

Brand:
Emeside
Epesri
Ethosuximide (generic)

Ethosuximide is a Category 3 medication and therefore it is usually unnecessary to be maintained on the same brand, however non-clinical factors such as patient’s anxiety need to be considered.

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31
Q

What are the main side effects associated with Ethosuximide?

A

GI disturbances
Anxiety
Sleep disturbances
Behavioural
Ataxia
Drowsiness
Rash (Steven Johnson syndrome)

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32
Q

What is the monitoring required for Ethosuximide therapy?

A

Therapeutic monitoring is not usually required only in pregnancy and renal impairment may you wish to request plasma-drug concentrations.

No specific ongoing monitoring (aside from patient self-monitoring of ADRs).

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33
Q

What are the key counselling points associated with Ethosuximide therapy?

A

Encourage patient self-monitoring and self-reported side effects indicating:

Skin disorders: including Steven-Johnson syndrome symptoms include ulcers of the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). Rashes are often preceded by influenza-like symptoms fever, headache, body ache (flu-like symptoms) and are most likely to occur within the first few months of treatment.

Blood dyscrasias: Bruising, bleeding, sore throat - request blood count

Ethosuximide is also associated with suicidal behaviour tendencies, may need to be reviewed and discontinued.

34
Q

What are the main pharmacokinetic parameters associated with Ethosuximide therapy?

A

Has good oral absorption and undergoes liver metabolism.
Not a CYP inhibitor or inducer.

35
Q

Are there any key interactions associated with Ethosuximide therapy?

A

Doesn’t interact with any other AEDs - possibly Carbamazepine however this has not been well studied.
No listed drug interactions in the BNF

36
Q

Are formulations of Ethosuximide bioequivalent?

A

Believe that they are bioequivalent

37
Q

In which type of epilepsy is Lamotrigine indicated?

A

First line monotherapy and add on:
Focal seizures
Generalised tonic-clonic seizures
Absent seizures (unsuccessful treatment with Sodium Valproate/Ethosuximide)
Tonic or atonic
Idiopathic generalised epilepsy

Second line and third line treatment:
Myoclonic (caution as can exacerbate)

Option for other epilepsy syndromes

38
Q

Aside from epilepsy, what are the other indications of Lamotrigine?

A

Bipolar disorder (monotherapy or add on)
Neuropathic pain (unlicensed)

39
Q

What formulations and brands of Lamotrigine are available? Can you switch?

A

Formulations:
Oral tablet
Dispersible tablet

Brands:
Lamotrigine
Lamictal

Lamotrigine is a Category 2 AED and therefore ideally the patient should be maintained on the same brand based on clinical and non-clinical factors. However if the brand needs to be switched a consultation with the patient should be done first with respect to clinical judgement such as previous history and seizure frequency.

40
Q

What are the main side effects associated with Lamotrigine?

A

Dizziness
Drowsiness
Headaches
Dry mouth
Diplopia (double vision)
Rash (more common when used in combination with other AEDs or rapid dose titration)
Hypersensivity syndrome
Suicidal thoughts
Blood disorders

41
Q

What is the monitoring required for Lamotrigine therapy?

A

No routine recommended monitoring - either therapeutic or toxic aside from self-monitoring for ADRs.

42
Q

What are the key counselling points associated with Lamotrigine therapy?

A

Encourage patient’s own self-monitoring for:

Skin reactions:
Warn patients and carers to see their doctor immediately if rash or signs or symptoms of hypersensitivity syndrome develop.

Blood disorders:
Patients and their carers should be alert for symptoms and signs suggestive of bone-marrow failure, such as anaemia, bruising, or infection. Aplastic anaemia, bone-marrow depression, and pancytopenia are not as associated.

43
Q

What are the main pharmacokinetic parameters associated with Lamotrigine?

A

The half life of Lamotrigine is altered with CYP inhibitors and inducers and the dose should be adjusted accordingly.
Whilst Lamotrigine does not affect other AEDs it does auto-induce its own metabolism, again affecting its half life but is classed as a non-enzyme inducer.

44
Q

Are there any key interactions associated with Lamotrigine?

A

Other drugs also causing sedation
Lamotrigine potentially increases the concentration of Carbamazepine and Carbamazepine decreases the concentration of Lamotrigine. (Adjust Lamotrigine dose and monitor Carbamazepine concentration).
Desmopressin, severe risk of hyponatremia
CYP inhibitors and inducers alter half-life and therefore concentration of Lamotrigine

45
Q

Are formulations of Lamotrigine bioequivalent?

A

There is no information to suggest that the two formulations are not bioequivalent.

46
Q

In which type of epilepsy is Levetiracetam indicated?

A

First line monotherapy in:
Generalised tonic-clonic (for women of childbearing potential)
Focal seizures
Myoclonic seizures
Idiopathic generalised seizures

Second line monotherapy:
Absent seizures
Myoclonic seizures
Idiopathic generalised seizures
Other epilepsy syndromes

Add on:
Focal seizures
Generalised tonic-clonic seizures
Myoclonic seizures

47
Q

What formulations and brands of Levetiracetam are available? Can you switch?

A

Formulation:
Oral tablet
Oral solution
Granules for oral solution
Oral granules
Solution for infusion

Brand:
Levetiracetam
Keppra
Eltam
Desitrend

Levetiracetam is a Category 3 medication and therefore it is usually unnecessary to be maintained on the same brand, however non-clinical factors such as patient’s anxiety need to be considered.

48
Q

What are the main side effects associated with Levetiracetam?

A

Drowsiness
Dizziness
Anxiety
GI disturbances
Asthenia (lack of energy)
Insomnia
Behavioural abnormalities (aggression, irritability)
Rash

Uncommon/rare side effects:
Suicidal behaviours
Thrombocytopenia
Leukopenia

49
Q

What is the monitoring required for Levetiracetam therapy?

A

No specific monitoring is required however you would monitor the plasma- drug concentration in pregnancy as they decrease during pregnancy (by up to 60% in the third trimester).
During other physiological changes such as puberty, aging in addition to renal impairment to avoid toxic levels.

50
Q

What are the key counselling points associated with Levetiracetam therapy?

A

Encourage patients to report if they are experiencing any suicidal behaviours as this will prompt a medication review.

Patients and carers should be cautioned on the effects on driving and performance of skilled tasks—increased risk of somnolence or other CNS side-effects

51
Q

What are the main pharmacokinetic parameters associated with Levetiracetam?

A

High oral bioavailability near to 100%
Linear pharmacokinetics therefore a predictable plasma concentration
Not extensively metabolised with the majority excreted through the kidney unchanged
Doesn’t undergo CYP metabolism - only hydrolysed
Is a non-enzyme inducer

52
Q

What are the main interactions associated with Levetiracetam?

A

Other drugs causing sedation
Decreases the clearance rate of MTX

53
Q

Are the formulations of Levetiracetam bioequivalent?

A

No evidence to demonstrate that they are not.

54
Q

In which type of epilepsy is Phenobarbital indicated?

A

Not first line for any types of seizures

Second-line add on therapy in:
Generalised tonic-clonic

Third line add on therapy in:
Focal seizures
Myoclonic seizures

Licensed for all types except typical absence seizures as stated.
IV formulation used in Status Epilepticus

55
Q

What formulations and brands of Phenobarbital are available? Can you switch?

A

Formulations:
Oral tablet
Oral solution
Solution for injection

Brand:
Only generic Phenobarbital

Phenobarbital is Category 1 AED and therefore patient’s should be maintained on a specific brand as there are clinically relevant differences between brands. Increasing the potential for adverse effects and risk of loss of seizure control.

56
Q

What are the potential side effects of Phenobarbital?

A

Steven-Johnson syndrome
Bone fracture risk and bone disorders
Blood disorders
Folate deficiency
Drowsiness
Suicidal behaviours
Hepatic disorders

Also associated with anti-epileptic hypersensivity syndrome

57
Q

What is the monitoring required for Phenobarbital therapy?

A

Therapeutic monitoring:
Plasma-phenobarbital concentration for optimum response is 15–40 mg/litre (60–180 micromol/litre); however, monitoring the plasma-drug concentration is less useful than with other drugs because tolerance occurs.

58
Q

What are the key counselling points for Phenobarbital therapy?

A

Encourage patients to report if they are experiencing any suicidal behaviours as this will prompt a medication review.

Encourage self-monitoring for:
Skin disorders: including Steven-Johnson syndrome symptoms include ulcers of the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes). Rashes are often preceded by influenza-like symptoms fever, headache, body ache (flu-like symptoms) and are most likely to occur within the first few months of treatment.

59
Q

What are the main pharmacokinetic parameters associated with Phenobarbital?

A

Metabolism of Phenobarbital varies in neonates and in children
It is partly metabolised in the liver, some is excreted unchanged from the kidney
Is able to cross the placenta barrier and is also present in breast milk
Is a CYP450 inducer

60
Q

What are the main interactions associated with Phenobarbital?

A

Drugs that are CYP450 metabolised (decreasing plasma concentrations/exposure)
Drugs causing sedation

61
Q

Are the formulations of Levetiracetam bioequivalent?

A

No evidence to suggest otherwise.

62
Q

In which type of epilepsy is Phenytoin indicated?

A

No first line indications

Third line add on therapy:
Focal seizures

BNF indications include tonic-clonic and focal seizures however NICE states that if myoclonic or absent seizures are present they should not be used.
BNF states: use in prevention of seizures during or following neurosurgery or following severe head injury.

63
Q

Aside from epilepsy, what are the other indications of Phenytoin?

A

Trigeminal neuralgia (unlicensed) only initiated by a specialist

64
Q

What formulations and brands of Phenobarbital are available? Can you switch?

A

Formulations:
Oral tablet
Chewable tablet
Oral capsule
Oral suspension
Solution for injection

Brand:
Phenytoin sodium
Dilantin Infatabs / Suspension
Epanutin Infatabs / Suspension

Phenytoin is Category 1 AED and therefore patient’s should be maintained on a specific brand as there are clinically relevant differences between brands. Increasing the potential for adverse effects and risk of loss of seizure control.

65
Q

What are the potential side effects of Phenytoin?

A

Drowsy
Confused
Hiruitism
Gingival hyperplasia (overgrowth of gums)
Cerebellar dysfunction
Bone and bone marrow disorders (Haematopoietic system affected)
Megaloplastic anaemia

66
Q

What plasma concentration is associated with Phenytoin toxicity?

A

Above 20mg/litre

67
Q

What are some of the symptoms that indicate Phenytoin toxicity?

A

Nystagmus (repetitive, involuntary movements of the eyes)
Diplopia (double vision)
Ataxia
Confusion
Hyperglycaemia
Slurred speech

68
Q

What is the monitoring required for Phenytoin therapy?

A

Pre-screening also required for HLA-B*1502 allele (like Carbamazepine)

Therapeutic monitoring of trough drug-plasma concentration:
Reference range of 10-20 mg/litre

Elderly, pregnancy and when counteracting medications are used, frequency of therapeutic monitoring may be increased as well as careful interpretation of the total plasma-phenytoin concentration is necessary; it may be more appropriate to measure free plasma-phenytoin concentration.

Ongoing monitoring:
FBC - blood dyscrasias
IV use both ECG and BP should be monitored

69
Q

What are the key counselling points for Phenytoin therapy?

A

Monitor for signs of Phenytoin toxicity and signs of anti-epileptic hypersensivity syndrome.

Patients or their carers should be told how to recognise signs of blood or skin disorders, and advised to seek immediate medical attention if symptoms such as fever, rash, mouth ulcers, bruising, or bleeding develop. Leucopenia that is severe, progressive, or associated with clinical symptoms requires withdrawal.

70
Q

What are the main pharmacokinetic parameters associated with Phenytoin?

A

Phenytoin is highly protein bound (90%)
Phenytoin has a non-linear pharmacokinetic profile as there is saturation of the clearance pathways at therapeutic dosages, impacting the half-life.
Phenytoin is a CYP 450 inducer

71
Q

What is the impact of non-linear pharmacokinetic profile of Phenytoin?

A

It is not possible to predict the effect of dose increases on the plasma concentration of the drug.
Small dosage increases in some patients may produce large increases in plasma-drug concentration with acute toxic side-effects. Similarly, a few missed doses or a small change in drug absorption may result in a marked change in plasma-drug concentration.

72
Q

What are the main interactions of Phenytoin?

A

Drugs metabolised by CYP450 (decreasing exposure of the drugs)
Drugs causing sedation
Amiodarone increases the exposure of Phenytoin
Carbamazepine affects the concentration of Phenytoin and Phenytoin decreases the concentration of Carbamazepine.

73
Q

Are the formulations of Phenytoin bioequivalent?

A

Preparations containing phenytoin sodium are not bioequivalent to those containing phenytoin base (such as Epanutin Infatabs® and Epanutin® suspension); 100 mg of phenytoin sodium is approximately equivalent in therapeutic effect to 92 mg phenytoin base.

Plasma-drug concentrations are required when switching formulations as it can produce clinically significant differences.

74
Q

What factors would you want to check before interpretating a Phenytoin level?

A

Check patient’s adherence to their medication, Phenytoin has a half life of 22 hours - missing a dose could have significant effects due to non-linear pharmacokinetics
Check patient’s albumin level as 90% of Phenytoin is highly protein bound and therefore changes in albumin level can significantly affect ‘free Phenytoin level’
Assess the timing of the blood sample collection as it must be ensured that the blood sample is taken at the correct time relative to last Phenytoin dose, usually trough levels are measured.
Double check any recent dose changes or formulation changes due to not being bioequivalent
Check if the patient has recently started taking any medication, other CYP450 inducers such as Carbamazepine, Alcohol, Barbiturates, Theophylline and Rifampin, cause increase in metabolism of Phenytoin and therefore lower plasma concentrations.

75
Q

What are the Category 1 AEDs?

A

Carbamazepine
Phenobarbital
Phenytoin
Primidone

76
Q

What does it mean for the drug to be Category 1 AED?

A

The patient’s medication should be prescribed by brand as there are clinically relevant differences between brands, which if switched without close supervision and by a specialist can increase adverse effects and result in a loss of seizure control.

77
Q

What are the Category 2 AEDs?

A

Clobazam
Clonazepam
Eslicarbazapine
Lamotrigine
Sodium Valproate
Oxacarbazepine
Perampenal
Rufinamide
Topiramate
Zonisamide

78
Q

What does it mean for a drug to be a Category 2 AED?

A

The need for a continued supply of a particular brand is based upon clinical judgement and consultation with the patient or carer taking into account clinical and non-clinical factors.

79
Q

What are the Category 3 AEDs?

A

Brivaracetam
Ethosuximide
Gabapentin
Lacosamide
Levetriacetam
Pregabalin
Tiagabine
Vigabatrin

80
Q

What does it mean for a drug to be a Category 3 AED?

A

Usually unnecessary to be maintained on a brand however there should be a consideration for non-clinical factors.

81
Q

What are some of the clinical factors that can influence choice of whether to maintain on a particular brand?

A

Seizure frequency
Treatment history
Implications of a breakthrough seizure (driving)

82
Q

What are some of the non-clinical factors that can influence choice of whether to maintain/switch from or on a particular brand?

A

Cause of anxiety in patient
Confusion
Loss of adherence

Epilepsy (6 decks)

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