primidone

Actions and spectrum

• Anticonvulsant activity: primidone acts as an anticonvulsant by increasing the threshold for seizure activity in the brain. It is thought to achieve this by enhancing the activity of GABA (gamma-aminobutyric acid), which is an inhibitory neurotransmitter in the brain.
• Sedative and hypnotic effects: primidone can cause sedation and drowsiness, especially when it is first started or when the dosage is increased. This can make it useful in the treatment of certain types of epilepsy, such as nocturnal seizures.
• Treatment of essential tremor: primidone is also used in the treatment of essential tremor, which is a movement disorder that causes rhythmic shaking of the hands, head, or voice. The exact mechanism of action for primidone in essential tremors is not well understood.
• Wide spectrum of efficacy: primidone is effective in treating a broad spectrum of seizures, including tonic-clonic seizures, partial seizures, myoclonic seizures, and absence seizures.
• Side effects: primidone can cause a range of side effects, including drowsiness, dizziness, ataxia, headache, nausea, and vomiting. Long-term use of the drug can lead to cognitive impairment and mood changes.
• Dosage and administration: primidone is typically administered orally in tablet form, with dosages ranging from 125mg to 750mg per day, depending on the patient’s age, weight, and the severity of the condition being treated. The medication is usually started at a low dose and gradually increased to achieve the desired therapeutic effect.

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined:

1-10%

Paresthesia

Vertigo

Dysarthria

Ataxia

Pediatric patients

Hyperactivity

Paradoxical excitement

Geriatric patients

Confusion

Excitement

Depression

 

Adverse effects that decrease with continued treatment

Ataxia

Headache

Nystagmus

Vertigo

Drowsiness

Irritability

Restlessness

Dizziness

Frequency Not Defined

Nausea

Constipation

Megaloblastic anemia

Hypocalcemia

Osteomalacia

Stevens-Johnson syndrome

Acute psychosis

Vomiting

Diarrhea

Hepatotoxicity

Rickets

Rash

 

Black box warning:

primidone has been associated with an increased risk of suicidal thoughts and behaviour. This risk may be higher in patients with a history of depression or other psychiatric disorders.

 

Contraindications:

• Hypersensitivity: primidone is contraindicated in patients who have a known hypersensitivity to the drug or its components. Hypersensitivity reactions can range from mild rash to more severe symptoms like anaphylaxis.
• Porphyria: primidone is contraindicated in patients with porphyria, a rare genetic disorder that affects the production of heme, an essential component of hemoglobin. The use of primidone can trigger a porphyria attack, which can be life-threatening.
• Liver disease: primidone can cause liver damage, and it is contraindicated in patients with significant liver impairment or active liver disease. Patients having history of liver disease or who are taking other medications that can cause liver damage should be monitored closely for signs of liver dysfunction.
• Respiratory depression: primidone can cause respiratory depression, especially when it is taken in combination with other medications that depress the central nervous system. Patients who are at risk for respiratory depression, or who are taking other respiratory depressants, should be monitored closely.
• Depression and suicidal ideation: primidone has an increased risk of suicidal thoughts and behavior, especially in patients with a history of depression or other psychiatric disorders.
• Pregnancy and breastfeeding: primidone should be used with caution while pregnancy and breastfeeding, as it can cross the placenta and enter into breast milk. The medication can cause harm to the developing fetus or nursing infant, and the benefits and risks should be carefully considered before use.
• Renal impairment: primidone is primarily eliminated by the kidneys, and patients with significant renal impairment may require a dosage adjustment to prevent accumulation of the drug.

Caution:

• Drug interactions: primidone can interact with other medications, including other anticonvulsants, benzodiazepines, and some antidepressants. These interactions can alter the effectiveness and safety of primidone, and patients should be monitored closely for potential side effects or changes in therapeutic response.
• Cardiovascular disease: primidone can cause changes in heart rate and blood pressure, and patients with a history of cardiovascular disease should be monitored closely while taking the medication.
• Elderly patients: Elderly patients may be more susceptible to the sedative and cognitive side effects of primidone, and a lower starting dose may be required. These patients should also be monitored closely for signs of overdose or other adverse effects.
• Withdrawal symptoms: Abrupt discontinuation of primidone can cause withdrawal symptoms, including seizures, anxiety, and tremors. Patients should be gradually tapered off the medication to avoid these symptoms.
• Blood disorders: primidone can cause blood disorders, including leukopenia, thrombocytopenia, and anemia. Patients should be closely monitored of these disorders, including fever, sore throat, and easy bruising or bleeding.
• Alcohol use: Alcohol can increase the sedative effects of primidone and can also increase the risk of liver damage. Patients should stop taking alcohol while taking primidone.
• Use in children: primidone is generally safe and effective in children, but caution should be exercised in young children, particularly those under the age of 5, who may be more sensitive to the sedative and cognitive side effects of the medication.

Comorbidities:

• Liver disease: primidone is metabolized by the liver, so it may be contraindicated or require dose adjustment in patients with liver disease.
• Respiratory depression: primidone can cause respiratory depression, particularly in patients with respiratory disease or other conditions that impair lung function.
• Cardiovascular disease: Primidone may cause changes in blood pressure and heart rate, so it should be used with caution in patients suffering from cardiovascular disease.
• Porphyria: primidone can trigger acute attacks of porphyria, a rare genetic disorder that affects the production of heme in the body.
• Depression or suicidal thoughts: primidone can cause depression and increase the risk of suicidal thoughts or behaviours, particularly in patients with a history of depression or other mental health conditions.
• Renal impairment: primidone and its metabolites are primarily excreted by the kidneys, so dose adjustment may be necessary in patients with renal impairment.

Pregnancy consideration: category D

Lactation: primidone can be excreted in breast milk and can be harmful to nursing infants. 

Pregnancy category:

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester.
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women.
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women.
• Category N: There is no data available for the drug under this category.

 

Pharmacology:

The mechanism of action of primidone and its metabolites is not well understood, but it is believed to be related to their ability to increase the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits the activity of neurons in the brain. This results in a decrease in the excitability of neurons, which can reduce the occurrence of seizures.

Pharmacodynamics:

The pharmacodynamics of primidone are related to its effects on the central nervous system (CNS), where it acts as an anticonvulsant and antiepileptic medication. By enhancing the activity of GABA, primidone reduces the excitability of neurons, which can reduce the occurrence of seizures.

Pharmacokinetics:

Absorption: primidone is well absorbed from the gastrointestinal tract after oral administration. The time to reach peak plasma concentration is usually 3 hours.

Distribution: primidone is widely distributed throughout the body, and it crosses the blood-brain barrier to exert its effects on the central nervous system. It is approximately 20% to 25% bound to plasma proteins.

Metabolism: primidone undergoes hepatic metabolism, primarily via the cytochrome P450 system. It is metabolized to its active metabolites, phenobarbital and phenylethylmalonamide (PEMA), both of which have anticonvulsant properties.

Elimination: primidone and its metabolites are primarily eliminated by the liver and excreted in the urine. The elimination half-life of primidone is approximately 10-12 hours.

 

Administration:

primidone is usually administered orally in the form of tablets. The tablets are typically taken with or without food, and they should be swallowed whole with a glass of water.

The dosage of primidone is usually determined based on the patient’s weight and the severity of their condition. The medication is typically administered in divided doses, with the goal of maintaining a therapeutic level of the medication in the bloodstream.

 

Patient information leaflet

Generic Name: primidone

Pronounced: (prim-i-done)

Why do we use promidone?

primidone is an anticonvulsant medication that is primarily used to treat seizures, including partial seizures and generalized tonic-clonic seizures. It is used in the treatment of essential tremor, a neurological disorder characterized by involuntary shaking of the hands, head, and voice.

In the treatment of seizures, primidone is often used in combination with other anticonvulsant medications to help control the frequency and severity of seizures. It may also be used as a single therapy in some cases.