Rufinamide

• Banzel^®

Pregnancy Category: C

Lactation: not known if excreted in breast milk; do not nurse

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Do not stop taking rufinamide without first talking to your healthcare provider. Stopping rufinamide suddenly can cause serious problems.

Rufinamide can cause serious side effects, including:

• Like other antiepileptic drugs, rufinamide may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempt to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.

• Rufinamide can also cause allergic reactions or serious problems which may affect organs and other parts of your body like the liver or blood cells. You may or may not have a rash with these types of reactions. Call your healthcare provider right away if you have any of the following:
  • swelling of your face, eyes, lips, or tongue
  • trouble swallowing or breathing
  • a skin rash
  • hives
  • fever, swollen glands, or sore throat that do not go away or come and go
  • swollen glands
  • yellowing of your skin or eyes
  • dark urine
  • unusual bruising or bleeding
  • severe fatigue or weakness
  • severe muscle pain
• Your seizures may happen more often or become worse.

Do not take rufinamide if you have a genetic condition called familial short QT syndrome, a problem that affects the electrical system of the heart.

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking rufinamide until you talk to your healthcare provider. Rufinamide taken with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not drive, operate heavy machinery, or do other dangerous activities until you know how rufinamide affects you. Rufinamide can slow your thinking and motor skills.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

You should not use this medicine if you have a severe liver disease, or a genetic heart rhythm disorder called "Short QT syndrome."

Do not stop using rufinamide suddenly or you may have increased seizures.

Some people have thoughts about suicide while taking seizure medication. Stay alert to changes in your mood or symptoms.

You should not use rufinamide if you are allergic to it, or if you have:

• a genetic heart rhythm disorder called "Short QT syndrome"; or

• severe liver disease.

To make sure rufinamide is safe for you, tell your doctor if you have:

• heart disease;

• liver disease;

• kidney disease (or if you are on dialysis); or

• a history of depression, mental illness, or suicidal thoughts or actions.

You may have thoughts about suicide while taking this medicine. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Do not start or stop taking seizure medication during pregnancy without your doctor's advice. Having a seizure during pregnancy could harm both mother and baby. Tell your doctor right away if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of rufinamide on the baby.

Rufinamide can make hormonal birth control less effective. Use a barrier form of birth control (condom or diaphragm with spermicide). Hormonal contraception (birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

Rufinamide may pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using rufinamide.

Rufinamide should not be given to a child younger than 1 year old.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Absorption

Bioavailability

Well absorbed following oral administration; peak plasma concentrations occur 4–6 hours after a dose.1 Extent of absorption decreases with increasing doses.1

Food

Food increased the extent of absorption and peak exposure of a single 400-mg dose by 34 and 56%, respectively.1

Under fed conditions, ≥85% of a single 600-mg dose was absorbed.1

Special Populations

Peak plasma concentrations and AUC are decreased by 16 and 29%, respectively, at 3 hours after a hemodialysis session.1

Distribution

Plasma Protein Binding

34% (mainly albumin).1 6

Elimination

Metabolism

Extensively metabolized, primarily via carboxylesterase-mediated hydrolysis of the carboxylamide group to an inactive acid derivative (GCP 47292).1 6 8 10 11 12 13 14 15 16 17 18 21 Metabolic pathways do not involve CYP isoenzymes and glutathione.1 6 8 10 12 16 18

Elimination Route

Eliminated principally in urine (85%), mostly as metabolites (≥66% as CGP 47292); only 2% of dose is excreted as unchanged drug.1 6 8 10 11 12 13 15 16 17 18 21

Half-life

Approximately 6–10 hours.1 6

Special Populations

Effect of hepatic impairment on pharmacokinetics not evaluated.1

Renal impairment (Clcr <30 mL/minute) does not substantially alter pharmacokinetics; hemodialysis may reduce exposure (see Absorption: Special Populations under Pharmacokinetics).1

Pharmacokinetics in pediatric patients 4–17 years of age similar to pharmacokinetics in adults.1

No clinically important pharmacokinetic differences between healthy geriatric individuals and younger healthy adults.1

• Importance of providing copy of written patient information (medication guide) each time rufinamide is dispensed.1 20 31 Importance of patients reading this information prior to taking the drug.1 31

• Risk of suicidality (anticonvulsants, including rufinamide, may increase risk of suicidal thoughts or actions in about 1 in 500 people).1 2 20 34 Importance of patients, family members, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one's life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).1 2 34

• Risk of multiorgan hypersensitivity reactions.1 34 Importance of notifying clinician if rash (with or without fever) occurs.1 34

• Importance of taking rufinamide only as prescribed.1 34

• Importance of taking rufinamide with food.1 31 Importance of informing patients that rufinamide scored tablets may be swallowed whole, broken in half, or crushed.1 31 Importance of instructing patients in proper techniques for administration of the oral suspension, including use of the bottle adapter and oral dosing syringe.1

• When applicable, advise patients that rufinamide oral suspension does not contain lactose, gluten, or carbohydrates and is dye-free.1

• Risk of sleepiness, difficulty with coordination, and dizziness; importance of advising patients to avoid driving or operating machinery until they gain experience with the drug's effects.1 21 Risk of additive CNS effects (e.g., sedation) if used with alcohol or other drugs that affect the CNS.1 21 34

• Importance of informing patients not to stop taking rufinamide without first talking to their clinician since stopping the drug suddenly can cause serious problems, including seizures.1 31 34

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of clinicians informing women about the existence of and encouraging enrollment in pregnancy registries (see Pregnancy under Cautions).1 Potential increased risk of pregnancy in women taking hormonal contraceptives; importance of discussing use of additional contraceptive methods.1 10 21

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., hepatic disease, depression, bipolar disorder), family history of suicidality or bipolar disorder, or current diagnosis or history of familial short QT syndrome.1 31 34

• Importance of advising patients of other important precautionary information.1 (See Cautions.)

In the U.S.

• Banzel

Available Dosage Forms:

• Suspension
• Tablet

Therapeutic Class: Anticonvulsant

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For rufinamide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to rufinamide or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of rufinamide in children younger than 1 year of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of rufinamide in the elderly. However, elderly patients are more likely to have age-related heart, kidney, or liver problems, which may require caution and an adjustment in the dose for patients receiving rufinamide.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking rufinamide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using rufinamide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Calcifediol
• Nifedipine
• Orlistat
• Piperaquine

Using rufinamide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Carbamazepine
• Desogestrel
• Dienogest
• Drospirenone
• Estradiol Cypionate
• Estradiol Valerate
• Ethinyl Estradiol
• Ethynodiol Diacetate
• Etonogestrel
• Fosphenytoin
• Lamotrigine
• Levonorgestrel
• Medroxyprogesterone Acetate
• Mestranol
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Phenobarbital
• Phenytoin
• Primidone
• Triazolam
• Valproic Acid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of rufinamide. Make sure you tell your doctor if you have any other medical problems, especially:

• Depression, history of or
• Heart rhythm problems (eg, shortened QT interval) or
• Leukopenia (low white blood cells) or
• Mental illness, history of—Use with caution. May make these conditions worse.

• Familial Short QT syndrome (heart rhythm problem)—Should not be used in patients with this condition.

• Liver disease, mild to moderate or
• Patients undergoing dialysis—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Liver disease, severe—Use is not recommended in patients with this condition.

Patients undergoing dialysis 3 hours postdosing displayed a decrease in AUC and Cmax of 29% and 16%, respectively. Consider adjusting dose for drug loss during dialysis.

Mild to moderate impairment (Child-Pugh score 5 to 9): Use with caution.

Severe impairment (Child-Pugh score 10 to 15): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use is not recommended.

No adjustment recommended

Administration advice:
-This drug can be administered whole, cut in half, or crushed and dissolved in a half glass of water.
-This drug should be taken with water.
-Shake the oral suspension well before every administration.
-This drug should be administered with food.