Primidone

Pregnancy category: D; continue use if pregnant; consider vitamin K supplementation for 1 month before birth

Lactation: Distributed in breast milk; discontinue if drug effects occur in nursing infant

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.

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.

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.

Suicidal Behavior And Ideation

Antiepileptic drugs (AEDS), including Mysoline, 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.

Table 1 : Risk by indication for antiepileptic drugs in the pooled analysis

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 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.

Usage In Pregnancy

To provide information regarding the effects of in utero exposure to Mysoline, physicians are advised to recommend that pregnant patients taking Mysoline 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 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.

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

Stopping primidone suddenly can cause serious problems.

Primidone can cause serious side effects, including:

Like other antiepileptic drugs, primidone 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

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 primidone without first talking to a healthcare provider.

• Stopping primidone 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.

Do not take primidone if you:

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

Warning:

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

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of primidone there are no specific foods that you must exclude from your diet when receiving primidone.

You should not use this medication if you are allergic to primidone or phenobarbital (Luminal, Solfoton), or if you have porphyria.

You may have thoughts about suicide while taking this medication. Tell your doctor if you have new or worsening depression or suicidal thoughts during the first several months of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits. Do not miss any scheduled appointments.

Before taking this medication, tell your doctor if you are allergic to any drugs, or if you are pregnant or breast-feeding.

Primidone may cause harm to an unborn baby, but having a seizure during pregnancy could harm both the mother and the baby. Do not start taking primidone during pregnancy without your doctor's advice.

If you become pregnant while taking primidone, do not stop taking it without telling your doctor. Seizure control is very important during pregnancy and the benefits of preventing seizures may outweigh any risks posed by taking primidone.

If you have taken primidone during pregnancy, be sure to tell the doctor who delivers your baby about your primidone use. Both you and the baby may need to receive medications to prevent excessive bleeding during delivery and just after birth.

Primidone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

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

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

• It is used to help control certain kinds of seizures.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how primidone affects you.
• Do not stop taking this medicine all of a sudden without calling your doctor. You may have a greater risk of seizures. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
• It may take several weeks to see the full effects.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Anemia, low white blood cell count, and low platelet count may rarely happen.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking primidone.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this medicine, call your doctor right away.

• Desoxyphenobarbital
• Primaclone

• Mysoline

Essential tremor

Data from a systematic review including 14 studies (3 randomized controlled trials, 9 crossover studies, and 2 case series) support the use of primidone for the treatment of essential tremor in some populations. Additional data may be necessary to further define the role of primidone in this condition. Based on the American Academy of Neurology (AAN) practice parameter for the treatment of essential tremor, primidone is effective for the treatment of limb tremor in essential tremor and is recommended in the management of this condition.

Refer to adult dosing.

Store at 20°C to 25°C (68°F to 77°F).

Applies to primidone: oral suspension, oral tablet

Along with its needed effects, primidone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking primidone:

• Shakiness and unsteady walk
• unsteadiness, trembling, or other problems with muscle control or coordination

• Unusual excitement or restlessness (especially in children and in the elderly)

• Chills
• cough or hoarseness
• fainting spells
• fever and sore throat
• fever with or without chills
• general feeling of tiredness or weakness
• irregular heartbeat
• lower back or side pain
• painful or difficult urination
• pale skin
• shortness of breath
• skin rash
• sores, ulcers, or white spots on the lips or in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking primidone:

• Confusion
• continuous, uncontrolled rolling eye movements
• double vision
• troubled breathing

Some side effects of primidone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Clumsiness or unsteadiness
• dizziness or lightheadedness
• feeling of constant movement of self or surroundings
• sensation of spinning

• Decreased sexual ability
• drowsiness
• loss of appetite
• mood or mental changes
• nausea or vomiting

Data not available

Data not available