Mysoline

1-10%

Dysarthria

Paresthesia

Ataxia

Vertigo

Pediatric patients

• Paradoxical excitement
• Hyperactivity

Geriatric patients

• Excitement
• Confusion
• Depression

Adverse effects that decrease with continued treatment

• Drowsiness
• Ataxia
• Irritability
• Headache
• Restlessness
• Nystagmus
• Dizziness
• Vertigo

Frequency Not Defined

Acute psychosis (rare)

Nausea

Vomiting

Constipation

Diarrhea

Megaloblastic (folate-deficiency) anemia

Hepatotoxicity

Hypocalcemia

Rickets (rare)

Osteomalacia (rare)

Rash

Stevens-Johnson syndrome (rare)

To treat psychomotor, focal, or grand mal seizures

• Patients 8 years of age or older should be treated with the following regimen:
• Days 1 to 3: 100 to 125 mg at bedtime.
• Days 4 to 6: 100 to 125 mg twice daily.
• Days 7 to 9: 100 to 125 mg three times daily.
• Day 10 to maintenance: 250 mg three or four times daily.
• The maximum dose is 2 g daily.
• It takes several weeks before the antiseizure effects of primidone are seen.

To treat partial seizures

• The initial dose is 125 mg at bedtime. Increase the dose by 125 mg every 3 days to 250 mg every 12 hours if needed. The maximum dose is 500 mg daily.

MYSOLINE
( My-so- lean)
(primidone) Tablets

Read this Medication Guide before you start taking MYSOLINE and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about MYSOLINE?

Do not stop taking MYSOLINE without first talking to your healthcare provider.

Stopping MYSOLINE suddenly can cause serious problems.

MYSOLINE can cause serious side effects, including:

Like other antiepileptic drugs, MYSOLINE 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
• attempts 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

How can I watch for early symptoms of suicidal thoughts and actions?

• 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.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop MYSOLINE without first talking to a healthcare provider.

• Stopping MYSOLINE suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).

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.

What is MYSOLINE?

MYSOLINE is a prescription medicine used alone or with other medicines to treat people with:

• generalized tonic-clonic (grand mal) seizures
• complex partial (psychomotor) seizures
• partial (focal) epileptic seizures.

Who should not take MYSOLINE?

Do not take MYSOLINE if you:

• have a genetic disorder called porphyria
• are allergic to phenobarbital

What should I tell my healthcare provider before taking MYSOLINE?

Before you take MYSOLINE, tell your healthcare provider if you:

• have or have had depression, mood problems or suicidal thoughts or behavior
• have any other medical conditions
• are pregnant or planning to become pregnant. MYSOLINE may harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking MYSOLINE. You and your healthcare provider will decide if you should take MYSOLINE while you are pregnant.
  • If you become pregnant while taking MYSOLINE, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334 . The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy.
• are breastfeeding or plan to breastfeed. MYSOLINE can pass into breast milk. Talk to your healthcare provider about the best way to feed your baby if you take MYSOLINE.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Taking MYSOLINE with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist each time you get a new medicine.

How should I take MYSOLINE?

Take MYSOLINE exactly as prescribed. Your healthcare provider will tell you how much MYSOLINE to take and when to take it.

• Your healthcare provider may change your dose. Do not change your dose without talking to your healthcare provider.
• Do not stop taking MYSOLINE without first talking to your healthcare provider. Stopping MYSOLINE suddenly can cause serious problems.
• If you take too much MYSOLINE, call your healthcare provider or local Poison Control Center right away.

What should I avoid while taking MYSOLINE?

• MYSOLINE can make you sleepy or dizzy. Do not drink alcohol or take other drugs that make you sleepy or dizzy while taking MYSOLINE without first discussing this with your healthcare provider. Taking MYSOLINE with alcohol or drugs 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 MYSOLINE affects you. MYSOLINE can slow your thinking and motor skills.

What are the possible side effects of MYSOLINE?

See “What is the most important information I should know about MYSOLINE?”.

MYSOLINE may cause other serious side effects including:

• Sleepiness that can be severe, especially when you first start taking MYSOLINE.
• MYSOLINE may rarely cause blood problems. Symptoms may include:
  • fever, swollen glands, or sore throat that come and go or do not go away
  • Frequent infections or an infection that does not go away
  • tiredness
  • shortness of breath
• MYSOLINE may rarely cause allergic reactions. Symptoms may include:
  • skin rash
  • hives
  • sores in your mouth
  • blistering or peeling skin

The most common side effects of MYSOLINE include:

• problems with walking and moving
• feelings of dizziness, spinning, or swaying (vertigo)

These are not all the possible side effects of MYSOLINE. For more information, ask your healthcare provider or pharmacist.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 .

How should I store MYSOLINE?

Store MYSOLINE at room temperature between 68°F to 77°F (20°C to 25°C) in a tight, light-resistant container

Keep MYSOLINE and all medicines out of the reach of children.

General Information about MYSOLINE

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use MYSOLINE for a condition for which it was not prescribed. Do not give MYSOLINE to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about MYSOLINE. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about MYSOLINE that is written for health professionals.

For more information, go to www.VALEANT.com or call 1-877-361-2719

What are the ingredients in MYSOLINE?

Active Ingredient: primidone

Inactive ingredients: microcrystalline cellulose, lactose monohydrate, methylcellulose, sodium starch glycolate, sodium lauryl sulfate, magnesium stearate, talc, purified water and ferric oxide yellow (250 mg tablet only)

The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions. Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistant or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to Mysoline and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.

Read the entire FDA prescribing information for Mysoline (Primidone)

• Valeant Pharmaceuticals North America LLC

Tell your healthcare provider if you are pregnant or planning to become pregnant. Mysoline may harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Mysoline. You and your healthcare provider will decide if you should take Mysoline while you are pregnant.

• If you become pregnant while taking Mysoline, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. You can enroll in this registry by calling 1-888-233-2334. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy.

If you take too much Mysoline, call your healthcare provider or local Poison Control Center right away.

Anticonvulsant; a structural analog of phenobarbital; related to barbiturate-derivative anticonvulsants.a b c d

Used alone or with other anticonvulsants (e.g., phenytoin, phenobarbital); a c d however, some clinicians do not recommend concurrent use of primidone and phenobarbital because of possible increased sedation.a

Generalized Seizures

Prophylactic management of tonic-clonic (grand mal) seizures, particularly those refractory to other anticonvulsant therapy.a c d

Prophylactic management of other partial seizures (e.g., those with autonomic symptoms), including atonic (also known as akinetic) seizures.a b

Partial Seizures

Prophylactic management of partial seizures with complex symptomatology (psychomotor seizures).a c d

Prophylactic management of other partial seizures, including focal seizures.a b c d

General

• Closely monitor patients receiving anticonvulsant therapy for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.d g h i (See Suicidality Risk under Cautions.)

• When primidone therapy is discontinued, withdraw the drug slowly to avoid precipitating seizures or status epilepticus.a b c d

• When a patient is transferred to primidone from another anticonvulsant, gradually increase primidone dosage over a period of at least 2 weeks while gradually decreasing dosage of the other anticonvulsant, to maintain adequate seizure control.a c

Administration

Oral Administration

Administer orally.a c d

Dosage

Adjust dosage carefully according to individual requirements and response.a c d In some cases, determination of blood concentrations of the drug may be needed to achieve optimal dosage adjustment.c d

May require several weeks of therapy before therapeutic efficacy can be assessed.c d

Pediatric Patients

Anticonvulsant-naive children <8 years of age: Initially, 50 mg at bedtime (days 1–3), increase to 50 mg twice daily (days 4–6), then increase to 100 mg twice daily (days 7–9).a c d Follow with a maintenance dosage of 125–250 mg 3 times daily or 10–25 mg/kg daily given in divided doses.a c d Alternatively, some clinicians recommend 1.25 g/m2 daily in 2–4 divided doses.a

Anticonvulsant-naive children ≥8 years of age: Initially, 100–125 mg at bedtime (days 1–3), increase to 100–125 mg twice daily (days 4–6), then increase to 100–125 mg 3 times daily (days 7–9).a c d Follow with a maintenance dosage of 250 mg 3 or 4 times daily.a c d Do not exceed 500 mg 4 times daily.a c d

Children ≥8 years of age receiving other anticonvulsants: Initially, 100–125 mg (primidone) at bedtime; increase dosage (primidone) slowly to maintenance level while gradually decreasing dosage of other anticonvulsant.c d Continue this regimen until satisfactory dosage achieved with the combination, or the other drug is withdrawn.c d If primidone monotherapy is the objective, gradually increase primidone dosage while decreasing dosage of the drug being discontinued over a period of at least 2 weeks.a c d

Adults

Anticonvulsant therapy-naive adults: Initially, 100–125 mg at bedtime (days 1–3), increase to 100–125 mg twice daily (days 4–6), then increase to 100–125 mg 3 times daily (days 7–9).a c d Follow with a maintenance dosage of 250 mg 3 or 4 times daily.a c d Do not exceed 500 mg 4 times daily.a c d

Adults receiving other anticonvulsants: Initially, 100–125 mg (primidone) at bedtime; increase dosage (primidone) slowly to maintenance level while gradually decreasing dosage of other anticonvulsant.c d Continue this regimen until satisfactory dosage is achieved with the combination, or the other drug is withdrawn.c d If primidone monotherapy is the objective, gradually increase primidone dosage while decreasing dosage of the drug being discontinued over a period of at least 2 weeks.a c d

Prescribing Limits

Pediatric Patients

Children ≥8 years of age: Maximum 2 g daily given in divided doses (e.g., 500 mg 4 times daily).a c d

Adults

Maximum 2 g daily given in divided doses (e.g., 500 mg 4 times daily).a c d

Special Populations

No special population dosage recommendations at this time.c d

Specific Drugs

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 this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of primidone in children.

Geriatric

No information is available on the relationship of age to the effects of primidone in geriatric patients.

Unusual excitement or restlessness may occur in elderly patients, who are usually more sensitive than younger adults to these effects of primidone.

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 this medicine, 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 this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Artemether
• Atazanavir
• Boceprevir
• Cobicistat
• Delamanid
• Delavirdine
• Elvitegravir
• Lopinavir
• Lumefantrine
• Lurasidone
• Maraviroc
• Nisoldipine
• Rilpivirine
• Ritonavir
• Telaprevir
• Tipranavir
• Voriconazole

Using this medicine 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.

• Abiraterone
• Afatinib
• Alfentanil
• Alprazolam
• Amobarbital
• Anisindione
• Apixaban
• Apremilast
• Aprobarbital
• Axitinib
• Bedaquiline
• Bosutinib
• Bromazepam
• Buprenorphine
• Butabarbital
• Butalbital
• Butorphanol
• Calcifediol
• Carisoprodol
• Ceritinib
• Chloral Hydrate
• Chlordiazepoxide
• Chlorzoxazone
• Clobazam
• Clonazepam
• Clorazepate
• Cobimetinib
• Codeine
• Daclatasvir
• Dantrolene
• Darunavir
• Deflazacort
• Diazepam
• Dicumarol
• Dihydrocodeine
• Dolutegravir
• Doxylamine
• Elbasvir
• Eslicarbazepine Acetate
• Estazolam
• Ethchlorvynol
• Etonogestrel
• Exemestane
• Fentanyl
• Flibanserin
• Flunitrazepam
• Flurazepam
• Grazoprevir
• Halazepam
• Hydrocodone
• Hydromorphone
• Idelalisib
• Ketazolam
• Levorphanol
• Linagliptin
• Lorazepam
• Lormetazepam
• Macitentan
• Medazepam
• Meperidine
• Mephenesin
• Mephobarbital
• Meprobamate
• Metaxalone
• Methadone
• Methocarbamol
• Methohexital
• Midazolam
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naloxegol
• Netupitant
• Nifedipine
• Nilotinib
• Nintedanib
• Nitrazepam
• Olaparib
• Orlistat
• Oxazepam
• Oxycodone
• Oxymorphone
• Panobinostat
• Pentazocine
• Pentobarbital
• Periciazine
• Phenindione
• Phenobarbital
• Phenprocoumon
• Piperaquine
• Pixantrone
• Ponatinib
• Prazepam
• Primidone
• Quazepam
• Remifentanil
• Rivaroxaban
• Romidepsin
• Saquinavir
• Secobarbital
• Simeprevir
• Sodium Oxybate
• Sufentanil
• Tacrolimus
• Tapentadol
• Tasimelteon
• Temazepam
• Thiopental
• Tofacitinib
• Tramadol
• Triazolam
• Ulipristal
• Valproic Acid
• Vandetanib
• Velpatasvir
• Venetoclax
• Vilazodone
• Vortioxetine
• Zolpidem

Using this medicine 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.

• Betamethasone
• Cannabis
• Carbamazepine
• Cortisone
• Ginkgo
• Hydrocortisone
• Lamotrigine
• Leucovorin
• Methylprednisolone
• Ospemifene
• Prednisolone
• Prednisone
• Rufinamide
• Tiagabine
• Triamcinolone
• Warfarin

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

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

• Asthma, emphysema, or chronic lung disease—Primidone may cause serious problems in breathing.

• Depression, history of or
• Hyperactivity (in children) or
• Kidney disease or
• Liver disease—Primidone may make these conditions worse.

• Porphyria (an enzyme problem)—Should not be used in patients with this condition.

It is very important that your doctor check your progress at regular visits while you are using this medicine to see if it is working properly and to allow for a change in the dose. Blood tests may be needed to check for any unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away. Your doctor may want you to join a pregnancy registry for patients taking a seizure medicine.

If you have been taking primidone regularly for several weeks, you should not suddenly stop taking it without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping completely.

This medicine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you, your child, or your caregiver notice any of these side effects, tell your doctor or your child's doctor right away.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests (such as the metyrapone and phentolamine tests) may be affected by this medicine.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for allergies or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Primidone may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Oral contraceptives (birth control pills) containing estrogen may not work properly if you take them while you are taking primidone. Unplanned pregnancies may occur. You should use a different or additional means of birth control while you are taking primidone. If you have any questions about this, check with your doctor.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Chemical name: 5-ethyldihydro-5-phenyl-4,6 (1H, 5H)-pyrimidinedione. Structural formula:

Mysoline* (primidone) is a white, crystalline, highly stable substance, M.P. 279-284°C. It is poorly soluble in water (60 mg per 100 mL at 37°C) and in most organic solvents. It possesses no acidic properties, in contrast to its barbiturate analog.

Mysoline 50 mg and 250 mg tablets contain the following inactive ingredients: Microcrystalline Cellulose, NF; Lactose, USP; Methylcellulose, USP; Sodium Starch Glycolate, NF; Talc, USP; Sodium Lauryl Sulfate, NF; Magnesium Stearate, NF; Water, USP, Purified.

Mysoline 250 mg tablets also contain Ferric Oxide Yellow, NF.

_______________________________________________________________________________

* Registered trademark of Valeant Pharmaceuticals North America LLC.

ACTIONS

Mysoline raises electro- or chemoshock seizure thresholds or alters seizure patterns in experimental animals. The mechanism(s) of primidone's antiepileptic action is not known.

Primidone per se has anticonvulsant activity as do its two metabolites, phenobarbital and phenylethylmalonamide (PEMA). In addition to its anticonvulsant activity, PEMA potentiates the anticonvulsant activity of phenobarbital in experimental animals.

The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions. Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistant or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to Mysoline and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.

NDC 66490-691-10

Rx Only

Mysoline®
(primidone tablets, USP)

ORIGINAL
TABLET
DESIGN &
FORMULATION

Dispense the
accompanying
Medication Guide
to each patient.

250 mg

SEALED FOR
YOUR PROTECTION

100 Tablets

VALEANT
Pharmaceuticals North America LLC

NDC 66490-690-10

Rx Only

Mysoline®
(primidone tablets, USP)

Dispense the
accompanying
Medication Guide
to each patient.

50 mg

SEALED FOR
YOUR PROTECTION

100 Tablets

VALEANT
Pharmaceuticals North America LLC