Download Carbamazepine VS Oxcarbazepine

Carbamazepine
VS
Oxcarbazepine
in the management of
trigeminal neuralgia
Introduction
Trigeminal neuralgia
Pathogenesis
• The exact cause of trigeminal neuralgia is
not fully understood.
Pathogenesis
A compression of the
nerve, usually caused by
vascular structures
Partially injured sensory
neurons
Hyperexcitable
Medication
Carbamazepine
Carbamazepine (Tegretol®)
• Drug of choice
• Highly effective
– Provide complete pain relief within a few days
• Mechanism  Ion channel blockers
Enhances GABA
• It nearly completely absorbed
when taken orally within 2-8 hours
Carbamazepine
• Recommended dosage
– Starting daily dose 2 x 100 mg
– Final daily dosage 400 – 800 mg
(200 – 1200 mg)
– To be taken with food
• The starting daily dose is low, (one to two
pills a day), which is gradually increased
until the pain is completely alleviated or
side effects occur.
Carbamazepine
• After initial control of pain for 6 to 8 weeks,
attempts should be made to titrate the dosage to
the lowest level that controls the pain or even
gradually withdraw the medication completely.
• A lowering of the dosage should be attempted
after a symptom-free period of 3 to 6 months.
• In the case of recurring symptoms, the dosage
has to be slowly increased until pain control is
achieved.
Carbamazepine
• Metabolized by the liver cytochrome P450
enzyme 3A4
– Produce a toxic epoxide metabolite
• Cause liver damage and anemia
• Induce the several cytochrome P450 enzyme
systems
• Result in multiple adverse effects including drug
interactions
– Transient
– Dose-dependant
• Need to be started at a low dose and increased
slowly in order to minimize side effects.
Carbamazepine
• Baseline laboratory studies are indicated
before and during the therapy
(monthly during the first year and quarterly thereafter)
– Complete hematologic and liver function
evaluation
– Complete blood cell count (CBC)
– Serum ion concentration, serum ionized
calcium concentration
– Plasma carbamazepine concentration
Adverse reactions
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Drowsiness
Dizziness
Confusion
Vertigo
Nausea
Vomiting
Hematologic side effects
– Agranulocytosis, Aplastic anemia, Leukopenia, Pancytopenia,
thrombocytopenia
• Hepatotoxic
• Stevens-Johnson syndrome and toxic epidermal
necrolysis (Asian individuals who carry the HLA-B*1502 allele)
Adverse reactions
• Gastrointestinal manifestations
– Abdominal pain, Diarrhea, Constipation, Anorexia, Stomatitis, Glossitis,
Dryness of the mouth & pharynx
• Skin manifestations
– Pruritus and erythematous rashes, Urticaria, Photosensitivity
• Nervous system
– Blurred or double vision, Nystagmus
• Cardiovascular system
– Aggravation of hypertension
• Respiratory system
– Pulmonary hypersensitivity
• Genitourinary system
– Oliguria
• Musculoskeletal system
– Arthralgia, Myalgia
Drug interactions
• Inhibit or enhance the potential of other
drugs
• Erythromycin
– Increase the plasma levels of carbamazepine
resulting in toxicity
• Warfarin
– Diminish the activity of warfarin through
increased metabolism
Medication
Oxcarbazepine
Oxcarbazepine (Trileptal®)
• Prodrug of carbamazepine
Carbamazepine
Oxcarbazepine
Oxcarbazepine (Trileptal®)
• Second-line drug
• Mechanism  Ion channel blockers
Enhances GABA
• It is well absorbed and peak levels are
reached within 2 hours.
• It is rapidly broken down to its
pharmacologically active form which is
then excreted through the kidneys.
Oxcarbazepine
• Other similarly effective drugs with potentially less
problematic side-effect profiles and risks of toxicity
• The side effects are less severe and less frequently
experienced.
• Not a strong inducer of the cytochrome enzymes 
more stable, fewer drug interactions
• This drug does not use the liver cytochrome system and
therefore does not result in such widespread drug
interactions and is generally better tolerated.
• However, be remembered that, given the chemical
similarity of these drugs, allergic cross-reactions
between the two drugs can occur
Adverse reactions
• Less nervous system side effects
• Common side effects are nausea,
vomiting, dizziness, ataxia, headache,
nystagmus, somnolence, diplopia, fatigue,
tremors, abdominal pain, and rhinitis.
• Less frequent symptoms are rash,
respiratory infections, double vision, and
changes in electrolytes in blood.
• Hyponatremia
Oxcarbazepine
• But must be taken in higher doses to provide
adequate pain control.
– 300 mg dose is equipotent to 200 mg of
carbamazepine
• The dose usually begins at 300 mg twice a day
and is gradually increased to achieve pain
control. (300 mg/day every 3 days)
• The effective dose ranges from 600-1200
mg/day.
• The maximum dose is 2400 mg per day.
Advantages over carbamazepine
• No monitoring of hematologic parameters
required
• Fewer drug-drug interactions
• No autoinduction of metabolism
• Comparable efficacy
• Improved tolerability
References
• Zakrzewska JM, McMillan R. Trigeminal neuralgia: the diagnosis and
management of this excruciating and poorly understood facial pain.
Postgrad Med J. 2011;87:410-6.
• Turp JC, Gobetti JP. Trigeminal neuralgia versus atypical facial pain
(A review of the literature and case report). ORAL SURG ORAL
MED ORAL PATHOL ORAL RADiOL ENDOD. 1996;81:424-32.
• Carrazana E, Mikoshiba I. Rationale and evident for the use of
oxcarbazepine in neuropathic pain. J Pain Symptom Manage.
2003;25:s31-5.
• Zakrzewska JM, Patsalos PN. Oxcarbazepine: a new drug in the
management of intractable trigeminal neuralgia. J Neurol Neurosurg
Psychiatry. 1989;52:472-6.
• Chole R, Patil R, Degwekar SS, Bhowate RR. Drug treatment of
trigeminal neuralgia: a systematic review of the literature. J Oral
Maxillofac Surg. 2007;65:40-5.
References
• Benoliel R, Sharav Y. Pharmacotherapy of chronic orofacial pain. In:
Sharav Y, Benoliel R, editor. Orofacial pain and headache. St. Louis:
Mosby; 2008. p. 377-405.
• Clark GT, Teruel A. Anticonvulsant agents used for neuropathic pain
including trigeminal neuralgia. In: Clark GT, Dionne RA, editor.
Orofacial pain a guide to medications and management. West
Sussex: Wiley-Blackwell; 2012. p. 95-114.
• Zakrzewska JM. Trigeminal neuralgia. In: Zakrzewska JM, Harrison
SD, editor. Assessment and management of orofacial pain, Pain
research and clinical management. Vol 14. Amsterdam: Elsevier;
2002. p. 267-369.