zonisamide

Zonisamide是一种抗癫痫药物使用adjunctive therapy for partial onsetseizuresin people withepilepsyolder than 16 years of age.

Seizuresare caused by abnormal electrical activity in the brain and partial or focalseizureis a type ofseizurein which the abnormal electrical activity is confined to a limited area of the brain. Zonisamide is also used off-label for binge-eating disorder, along withcognitive behavioral therapy分,因为它似乎抑制了需求er in the brain.

Zonisamide reduces the duration of focal seizures, prevents seizure spread to other regions of the brain, and increases the threshold for generalized seizures. Zonisamide is more effective for the tonic (rigidity) phase than the clonic (convulsion) phase of seizures. Zonisamide stabilizes the membranes of nerve cells (neurons) and suppresses neuronal hypersynchronization by reducing the inflow of sodium and calcium currents and the action potential. Zonisamide has no effect on the neurotransmitters gamma-aminobutyric acid (GABA) or glutamate.

• Do not use in patients with known hypersensitivity tosulfonamides, zonisamide, or any of its components. Although rare, fatal drug reactions have occurred. Reactions have included life-threatening skin reactions, multiorgan reactions, andblood disorders. Monitor the patient and discontinue zonisamide if hypersensitivity symptoms develop.
• Zonisamide can reducesweatingand dangerously increase body temperature in pediatric patients. Zonisamide is not approved for use in children under 16 years.
• Antiepilepticdrugsincluding zonisamide can increase the risk ofsuicidal thoughtsand behavior. Patients, their family and caregivers should be appropriately cautioned.
• Abrupt discontinuation of zonisamide may increase seizure frequency or precipitate status epilepticus, a state of prolonged seizure lasting longer than 5 minutes.
• Zonisamide causes fetal harm. Women of reproductive potential should be advised to use effectivecontraception.
• May cause metabolic acidosis in certain patients. Risk factors includekidney disease, severe respiratory disease,diarrhea, status epilepticus,ketogenic diet, and some drugs.
• Zonisamide can cause central nervous system (CNS) effects including psychiatric symptoms such asdepressionand psychosis, cognitive and speech problems,fatigue, and drowsiness. Patients should be cautioned to avoid performing tasks that require mental alertness.
• Zonisamide can increase ammonia level, which is neurotoxic and may damage the brain. The risk is higher in patients with inborn metabolic errors.
• Can causekidney stones. Advise patients to increase water intake.
• Can affect kidney function and increasecreatininelevels and blood urea nitrogen (BUN).
• Use zonisamide with caution in patients with impairedliveror kidney function.
• There are reports of ophthalmic effects including acutemyopia, angle closureglaucoma,ocularpain, and reduced visual acuity.

Common side effects of zonisamide include:

• Drowsiness (somnolence)
• Dizziness
• Headache
• Agitation
• Irritability
• Nausea
• Loss of appetite(anorexia)
• Abdominal pain
• Diarrhea
• Indigestion(dyspepsia)
• Constipation
• Vomiting
• Taste disorder(dysgeusia)
• Dry mouth(xerostomia)
• Weight loss
• Fatigue
• Tiredness
• Confusion
• Depression
• Anxiety
• Nervousness
• Difficulty concentrating
• Memory impairment
• Insomnia
• Mental slowing
• Difficulty with language (dysphasia)
• Speech disorder (dysarthria)
• Schizophrenic/schizophreniform behavior
• Impaired coordination, balance and speech (ataxia)
• Abnormal gait
• Weakness(asthenia)
• Numbness and tingling (paresthesia)
• Excessive sensitivity of skin (hyperesthesia)
• High temperature (hyperthermia)
• Low muscle tone (hypotonia)
• Tremor
• Seizure
• 圣atus epilepticus, a state of prolonged seizure
• Repetitive uncontrolled eye movements (nystagmus)
• Lazy eye(amblyopia)
• 复视(diplopia)
• Ringing in the ears(tinnitus)
• Excessive acidity of body fluids (metabolic acidosis)
• Flu-likesyndrome
• Accidental injury
• Increasedcough
• Throat inflammation (pharyngitis)
• Nasal inflammation (rhinitis)
• Kidney stones (nephrolithiasis)
• Facial swelling (edema)
• Skin reactions including:
  • Reducedsweating(hypohidrosis)
  • Bruisingand skin discoloration (ecchymosis)
  • Rash
  • Itching(pruritus)
  • 圣evens-Johnson syndrome
  • Toxic epidermal necrolysis

Less common side effects of zonisamide include:

• Chest pain
• Flankpain
• Feeling unwell (malaise)
• Allergic reaction
• Neck rigidity
• Gas(flatulence)
• Gum inflammation (gingivitis)
• Gum overgrowth (hyperplasia)
• Gum hemorrhage
• Gastrointestinal inflammation (gastritisandgastroenteritis)
• Oral and tongue inflammation (stomatitis and glossitis)
• Ulcerative stomatitis
• Gallstone (cholelithiasis)
• Black,tarry stools(melena)
• Rectal hemorrhage
• Gastro-duodenal ulcer
• Swallowing difficulty (dysphagia)
• Shortness of breath(dyspnea)
• Palpitation
• Rapid or slowheartrate (tachycardia/bradycardia)
• Vascular insufficiency
• Low orhigh blood pressure(hypotension/hypertension)
• Inflammation withblood clotin the vein (thrombophlebitis)
• Cerebrovascular accident
• Fainting(syncope)
• Peripheraledema
• Weight gain
• Thirst
• Dehydration
• Low blood count of leukocyte immune cells (leukopenia)
• Low red blood cell count(anemia)
• Immunodeficiency
• Lymph nodeswelling (lymphadenopathy)
• Leg cramps
• Muscle pain(myalgia)
• Muscle weakness (myasthenia)
• Joint pain(arthralgia)
• Joint inflammation(arthritis)
• Inflammation ofconjunctiva, the membrane over the eye whites and innereyelidsurfaces (conjunctivitis)
• Visual field defect
• Glaucoma, an eye disease with highintraocular pressurethat damages theoptic nerve
• Deafness
• Loss of smell(parosmia)
• High muscle tone (hypertonia)
• Twitching
• Vertigo
• Excessive movement and restlessness (hyperkinesia)
• Movement disorder (dyskinesia)
• Abnormal dreams
• Euphoria
• Increased reflexes
• Nerve damage (neuropathy)
• Peripheral nerve inflammation (neuritis)
• Decreased libido
• Impotence
• Absence ofmenstruation(amenorrhea)
• Urinary frequency
• Urinary incontinence
• Urinary urgency
• Excessive urination (polyuria)
• Frequent nighttime urination (nocturia)
• Painful urination(dysuria)
• Blood in urine(hematuria)
• Urinary retention
• Dry skin
• Acne
• Hives(urticaria)
• Eczema
• Eruptive skinrasheswith pustules orblisters
• Hair loss(alopecia)
• Abnormal male pattern hair growth in women (hirsutism)

Rare side effects of zonisamide include:

• Lupuserythematosus, an autoimmune condition
• Rapid and irregular atrial rhythm (atrial fibrillation)
• Extra beats in the ventricles (ventricular extrasystoles)
• 心failure
• Blood clotinlungs(pulmonary embolism)
• Inflammation of the gall bladder or bile ducts (cholecystitis/cholangitis)
• Jaundicefrom impaired bile flow (cholestaticjaundice)
• Blood in vomit (hematemesis)
• Esophagus, duodenum or colon inflammation (esophagitis/duodenitis/colitis)
• Acute pancreas inflammation (pancreatitis)
• Fecal incontinence
• Anemiadue tored cellsbeing smaller than normal (microcytic anemia)
• Low count of platelets (thrombocytopenia)
• Low blood sugarlevels (hypoglycemia)
• Low sodium levels (hyponatremia)
• Increase in lactic dehydrogenase (LDH) enzyme
• Increase inliver enzymesSGOT and SGPT
• Pause inbreathing(apnea)
• Coughing up blood(hemoptysis)
• Suicidalthoughts and behavior
• Numbness and tingling around the mouth (circumoral paresthesia)
• Facialparalysis
• Eyemuscle spasm(oculogyric crisis)
• Light sensitivity (photophobia)
• Inflammation of theiris(iritis)
• Acute shortsightedness (myopia) and secondary angle closure glaucoma
• Excessive albumin in urine (albuminuria)
• Bladder pain
• Bladder stone (calculus)
• Breast tissue growth in males (gynecomastia)
• Breast inflammation (mastitis)
• Excessive menstrual bleeding (menorrhagia)
• Breakdown of muscle cells (rhabdomyolysis)
• Increase in creatine phosphokinase
• Drug reaction with eosinophilia and systemic symptoms (DRESS)
• 血液中氨含量高(hyperammonemia)andbrain damage(encephalopathy)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Seriousheart symptoms包括英足总st or pounding heartbeats, fluttering in your chest, shortness of breath, and suddendizziness;
• Severeheadache, confusion, slurred speech, severe weakness,vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, highfever, sweating, confusion, fast or uneven heartbeats,tremors, and feeling like you might pass out; or
• Serious eye symptoms includeblurred vision,tunnel vision,eye painor swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Capsule

• 25 mg (Zonegran; generic)
• 100 mg (Zonegran; generic)

Oral Suspension

• 100 mg/5mL (Zonisade)

成人:

Partial Seizures

• Indicated as adjunctive therapy for partial seizures
• Initial: 100 mg orally every day
• Increase to 200 mg/day after 2 weeks (may divide dose twice a day); may increase further by increments of 100 mg/day after a minimum of 2 weeks between adjustments; not to exceed 600 mg/day
• Usual effective dose: 100-600 mg/day

Binge-eating Disorder (Off-label)

• Initial: 100 mg orally every day
• May increase by 100 mg increments every 2 weeks; not to exceed 600 mg/day (may divide every 12 hours after the first week)

Geriatric:

Partial Seizures

• Administer as in adults; initiate dosing at the lower end of the dosing range

Pediatric:

Partial Seizures

Indicated as adjunctive therapy for partial seizures in adolescents aged 16 years and above

Children below 16 years

• Safety and efficacy not established
• Cases of oligohidrosis and hyperpyrexia have been reported

Children 16 years and above

• Initial: 100 mg orally every day
• Increase to 200 mg/day after 2 weeks (may divide dose twice a day); may increase further by increments of 100 mg/day after minimum of 2 weeks between adjustments; not to exceed 600 mg/day
• Usual effective dose: 100-600 mg/day

Dosage Modifications (Adult and Pediatric)

Renal impairment

• Titrate dose more slowly and frequently monitor
• GFR less than 50 mL/min: Avoid use
• Discontinue ifacute renal failuredevelops or clinically significant sustained increase in creatinine/BUN

Hepatic impairment

• Not studied

• Zonisamide overdose can cause central nervous system (CNS)depressionwithlow blood pressure(hypotension), slow heart rate (bradycardia), respiratorydepression, andcoma.
• 过量treatment includes maintenance ofairway, induced vomiting, or gastric lavage to clear undigested stomach contents, and supportive care with frequent monitoring of vital signs.

Inform your doctor of all medications you are currently taking, who can advise you on any possibledrug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Zonisamide has no known severe interactions with other drugs.
• Serious interactions of zonisamide include:
  • abametapir
  • apalutamide
  • fexinidazole
  • idelalisib
  • ivosidenib
  • lonafarnib
  • metoclopramideintranasal
  • nefazodone
  • tucatinib
  • voxelotor
• Zonisamide has moderate interactions with at least 48 different drugs.
• Zonisamide has mild interactions with at least 73 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription andover-the-countermedications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Women of reproductive potential should use effective contraception during zonisamide therapy and for one month after discontinuation.
• There are no adequate and well-controlled studies on use of zonisamide inpregnantwomen, however, animal reproductive studies show evidence of fetal malformations and loss ofpregnancy.
• Zonisamide should be used inpregnantwomen at the lowest effective doses, only if potential benefits to the mother outweigh potential risks to the fetus.
• Zonisamide is known to cause metabolic acidosis.Newborninfants exposed to zonisamide should be monitored for metabolic acidosis after birth.
• Zonisamide is present inbreast milkand has potential for causing serious adverse reactions in thebreastfedinfant. Based on the importance of the drug to the mother, decision should be made to discontinue the drug ornursing.
• A registry is available for women exposed to zonisamide duringpregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 orhttps://www.aedpregnancyregistry.org/).

• Take zonisamide exactly as prescribed.
• 圣ore zonisamide safely out of reach of children.
• In case of overdose, seek medical help immediately or contactPoison Control.
• Zonisamide can impair mental and physical abilities, avoid engaging in hazardous activities such as driving and operating heavy machinery until the drug effects can be determined.
• Contact your physician immediately if you develop any of the following conditions:
  • Skinrashor if your seizures worsen
  • Fever,sore throat, oral ulcers, oreasy bruising
  • Severe muscle pain or weakness
• Contact your physician if you notice your child sweating less than usual, with or without fever.
• Zonisamide can cause kidney stones, increase your water intake during therapy. Contact your physician if you havesymptoms of kidney stone, such as suddenback pain,abdominal painorblood in urine.
• Zonisamide may induce depression andsuicidalthoughts. Seek support from family, friends and your healthcare provider if you feeldepressed.
• If you are a family member orcaregiverof a patient on zonisamide therapy, be alert for signs and symptoms of depression and contact the healthcare provider if you notice unusual changes in the patient’s behavior.