Mysoline Information
Mysoline (Primidone) Description
Chemical name: 5-ethyldihydro-5-phenyl-4,6 (1H, 5H)-pyrimidinedione. Structural formula:
Mysoline (Primidone) * (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 (Primidone) 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 (Primidone) 250 mg tablets also contain Ferric Oxide Yellow, NF.
_______________________________________________________________________________
* Registered trademark of Valeant Pharmaceuticals North America.
Mysoline (Primidone) Indications And Usage
Mysoline (Primidone) , used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy.
Mysoline (Primidone) Contraindications
Primidone is contraindicated in: 1) patients with porphyria and 2) patients who are hypersensitive to phenobarbital (see ).
Mysoline (Primidone) Warnings
The abrupt withdrawal of antiepileptic medication may precipitate status epilepticus. The therapeutic efficacy of a dosage regimen takes several weeks before it can be assessed.
Antiepileptic drugs (AEDS), including Mysoline (Primidone) , increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.
Table 1 shows absolute and relative risk by indication for all evaluated AEDs.
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Mysoline (Primidone) or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
To provide information regarding the effects of in utero exposure to Mysoline (Primidone) , physicians are advised to recommend that pregnant patients taking Mysoline (Primidone) enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
The effects of Mysoline (Primidone) in human pregnancy and nursing infants are unknown.
Recent reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.
The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship.
There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors leading to birth defects, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorders are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.
The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. Pregnant women under anticonvulsant therapy should receive prophylactic vitamin K1 therapy for one month prior to, and during, delivery.
Mysoline (Primidone) Precautions
The total daily dosage should not exceed 2 g. Since Mysoline (Primidone) therapy generally extends over prolonged periods, a complete blood count and a sequential multiple analysis-12 (SMA-12) test should be made every six months.
Suicidal Thinking and Behavior - Patients, their caregivers, and families should be counseled that AEDs, including Mysoline (Primidone) , may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see section).
Please refer to the Mysoline (Primidone) Medication Guide provided with the product for more information.
Mysoline (Primidone) Adverse Reactions
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 (Primidone) and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.
Mysoline (Primidone) Dosage And Administration
Patients 8 years of age and older who have received no previous treatment may be started on Mysoline (Primidone) according to the following regimen using either 50 mg or scored 250 mg Mysoline (Primidone) tablets:
Days 1 to 3: 100 to 125 mg at bedtime.Days 4 to 6: 100 to 125 mg b.i.d.Days 7 to 9: 100 to 125 mg t.i.d.Day 10 to maintenance: 250 mg t.i.d.
For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg Mysoline (Primidone) tablets in divided doses (250 mg t.i.d. or q.i.d.). If required, an increase to five or six 250 mg tablets daily may be made but daily doses should not exceed 500 mg q.i.d.
Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5 to 12 μg/mL.
For children under 8 years of age, the following regimen may be used:
Days 1 to 3: 50 mg at bedtime.Days 4 to 6: 50 mg b.i.d.Days 7 to 9: 100 mg b.i.d.Day 10 to maintenance: 125 mg t.i.d. to 250 mg t.i.d.
For children under 8 years of age, the usual maintenance dosage is 125 to 250 mg three times daily or, 10 to 25 mg/kg/day in divided doses.
Mysoline (Primidone) How Supplied
Each square-shaped, scored, yellow tablet, identified by "Mysoline (Primidone) 250" and an embossed M, contains 250 mg of primidone, in bottles of 100 (NDC 66490-691-10)
Each square-shaped, scored, white tablet, identified by "Mysoline (Primidone) 50" and an embossed M, contains 50 mg of primidone, in bottles of 100 (NDC 66490-690-10)
The appearance of these tablets is a trademark of Valeant Pharmaceuticals North America.
Manufactured by: Plot No. 67-70, Sector - 2, Pithampur, 454775,Dist. Dhar, Madhya Pradesh, INDIA
Distributed by: One EnterpriseAliso Viejo, CA 92656 U.S.A.
Part No. EM 10142/bRev. 07/10
Mysoline (Primidone) Medication Guide
Read this Medication Guide before you start taking Mysoline (Primidone) 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.
Stopping Mysoline (Primidone) suddenly can cause serious problems.
Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
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.
Mysoline (Primidone) is a prescription medicine used alone or with other medicines to treat people with:
Do not take Mysoline (Primidone) if you:
Before you take Mysoline (Primidone) , tell your healthcare provider if you:
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.
Take Mysoline (Primidone) exactly as prescribed. Your healthcare provider will tell you how much Mysoline (Primidone) to take and when to take it.
Mysoline (Primidone) may cause other serious side effects including:
The most common side effects of Mysoline (Primidone) include:
These are not all the possible side effects of Mysoline (Primidone) . 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.
Store Mysoline (Primidone) at room temperature between 68ºF to 77ºF (20ºC to 25ºC) in a tight, light-resistant container
Keep Mysoline (Primidone) and all medicines out of the reach of children.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Mysoline (Primidone) for a condition for which it was not prescribed. Do not give Mysoline (Primidone) 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 (Primidone) . If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Mysoline (Primidone) that is written for health professionals.
For more information, go to www.VALEANT.com or call 1-877-361-2719
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)
VALEANT Pharmaceuticals North AmericaAliso Viejo, CA 92656
Issued July 2010
This Medication Guide has been approved by the U.S. Food and Drug Administration
Part No. EM 10142/bRev. 07/10
Mysoline (Primidone) Principal Display Panel - Mg Tablet Bottle Label
Mysoline (Primidone) Principal Display Panel - Mg Tablet Bottle Label
