perphenazine

Actions and Spectrum: 

perphenazine is a typical antipsychotic medication used to treat symptoms of schizophrenia and other psychotic disorders. Its action is not fully understood. Still, it is believed to work by blocking dopamine, serotonin receptors in the brain, which helps reduce the activity of specific nerve pathways responsible for causing hallucinations, delusions, and other psychotic symptoms. 

perphenazine belongs to the phenothiazine class of antipsychotics, and its spectrum of activity includes treating positive symptoms of schizophrenia, like hallucinations, delusions, and disordered thinking. It may also effectively treat negative symptoms of schizophrenia, such as lack of motivation and emotional flatness. However, it is generally less effective for these symptoms than some other antipsychotic medications. 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Frequency defined 

>10% 

Akathisia (60%) 

Frequency not defined 

Diminished gag reflex 

Confusion 

EPS 

Tardive dyskinesia 

Dystonia 

Neuroleptic malignant syndrome 

Muscle stiffness 

Akathisia (60%) 

Parkinsonism 

Rare 

Priapism 

Seizure 

Cholestatic jaundice 

Common 

Anticholinergic effects 

Sedation 

Erectile dysfunction 

Weight gain 

Oligomenorrhea 

Amenorrhea 

Less Common 

Lens opacities 

Orthostatic hypotension 

Anorexia 

Constipation 

Dyspepsia 

Ileus 

Tachycardia 

Weakness 

Anxiety 

Restless 

cerebral edema 

insomnia 

depression 

headache 

Uncommon 

Photosensitivity 

Pruritis 

Ejaculatory disorder 

Blood dyscrasia 

ECG changes 

Galactorrhea 

Diarrhea 

Black Box Warning: 

perphenazine has a black box warning for increased mortality in elderly patients with dementia-related psychosis. Older patients with dementia treated with antipsychotic medications, including perphenazine, are at an increased risk of death, especially during the first few months of treatment.

perphenazine is not approved for treating dementia-related psychosis, and its use in this population is associated with an increased risk of stroke, falls, and other adverse events. Physicians are advised to use caution when prescribing perphenazine to elderly patients with dementia-related psychosis and to carefully weigh the treatment’s potential benefits and risks before initiating therapy. 

Contraindication/Caution: 

Contraindication 

perphenazine is contraindicated in patients with hypersensitivity to perphenazine or other phenothiazines. It is generally not to use in patients with history of blood disorders, such as bone marrow depression, leukopenia, or agranulocytosis. Additionally, it should not generally be used in patients with a history of CNS (central nervous system) depression, comatose states, or in those who are in a state of acute alcohol intoxication or taking CNS depressants. 

perphenazine should be generally used with caution in patients with a previous history of seizures, liver or kidney disease, cardiovascular disease, or glaucoma. It should not be used during pregnancy condition or while breastfeeding unless the benefits outweigh the risks to the fetus or infant. 

As with all medications, healthcare professionals should carefully consider each patient’s unique medical history and medications before prescribing perphenazine to ensure that it is safe and appropriate for the patient. 

Caution 

perphenazine should be generally used cautiously in patients with a history of seizures, kidney or liver disease, cardiovascular disease, or glaucoma. It may also cause drowsiness or dizziness, impairing a patient’s ability to perform tasks that need mental alertness/coordination, such as driving or operating machinery. 

perphenazine may also increase the risk of developing a movement disorder typically known as tardive dyskinesia, which causes involuntary movements of the face and tongue. The risk of developing tardive dyskinesia may increase with long-term use of perphenazine, and the condition may not improve even after the medication is discontinued. 

perphenazine may also lower the seizure threshold and should be generally used cautiously in patients with a previous history of seizures or epilepsy. It might also interact with other medications, such as antihistamines, barbiturates, and benzodiazepines, to increase the risk of respiratory depression or sedation. 

Lastly, perphenazine may cause various side effects, including constipation, blurred vision, and urinary retention. These side effects may be managed with appropriate medical management and by adjusting the dose of the medication as needed. 

As with all medications, healthcare professionals should carefully consider each patient’s unique medical history and medications before prescribing perphenazine to ensure that it is safe and appropriate for the patient. 

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Yes 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology: 

perphenazine is a typical antipsychotic medication that blocks the dopamine receptors in the brain. Dopamine is a neurotransmitter that regulates motivation, mood, and movement. By blocking dopamine receptors, perphenazine reduces the activity of dopamine in certain regions of brain, which can help to diminish the symptoms of psychosis. 

perphenazine also antagonizes other neurotransmitters, including serotonin, histamine, and acetylcholine, which may contribute to its therapeutic effects. 

Pharmacodynamics: 

Mechanism of action: The antipsychotic medication obstructs the postsynaptic mesolimbic dopaminergic receptor in the brain. It exhibits moderate anticholinergic properties and weak-moderate sedative effects. The medication also produces powerful extrapyramidal effects while demonstrating potent antiemetic activity. 

Pharmacokinetics: 

Absorption 

perphenazine is well-absorbed after oral administration, and peak plasma concentrations are reached within 2-4 hours. The bioavailability of perphenazine is approximately 50% due to extensive first-pass metabolism in the liver. 

Distribution 

perphenazine is highly protein-bound (approximately 90%) and has a large volume of distribution, which allows it to rapidly distribute throughout the body, including the central nervous system. 

Metabolism 

perphenazine is extensively metabolized in the liver by the cytochrome P450 system, primarily via the CYP2D6 and CYP3A4 enzymes, to form several active and inactive metabolites. The primary active metabolite, called 7-hydroxyperphenazine, has similar pharmacological properties to perphenazine and may contribute to the overall therapeutic effects of the medication. 

Elimination and Excretion 

The elimination half-life of perphenazine is approximately 10-20 hours, and the duration of action may be prolonged with repeated dosing due to the accumulation of the medication in the body. Most perphenazine and its metabolites are excreted in the urine, with only a tiny percentage in the feces. 

Administration: 

Oral administration 

perphenazine is available in various formulations, including tablets, capsules, injectable solutions, and orally disintegrating tablets. The dose, duration of treatment will be based on the individual patient’s condition and response to treatment and should be determined by a healthcare professional. 

perphenazine tablets and capsules should be generally taken with a full glass of water, with/without food, as directed by the healthcare professional. The tablets should not be crushed/chewed, as this may affect the release of the medication. 

A healthcare professional should administer the injectable solution and be given deep intramuscularly into the upper outer quadrant of the buttock. The dose of the injectable solution may be adjusted based on the patient’s response to treatment and any adverse effects. 

The orally disintegrating tablets should be placed on the tongue and allowed to dissolve totally before swallowing. These tablets should not be chewed, crushed, or swallowed whole. 

Taking perphenazine as the healthcare professional prescribes is crucial, even if the patient feels better. Abruptly stopping the medication might cause withdrawal symptoms, and patients should only discontinue perphenazine under the supervision of their healthcare provider. 

If a dose is missed, it is normally recommended to take as early as possible. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.

Patient information leaflet 

Generic Name: perphenazine 

Pronounced: [ per-FEN-a-zeen ] 

Why do we use perphenazine? 

perphenazine is a typical antipsychotic medication primarily used to treat symptoms of schizophrenia and psychotic disorders. It effectively reduces positive symptoms of schizophrenia, such as hallucinations, delusions, and disordered thinking. 

In addition to schizophrenia, perphenazine may be used to treat psychiatric disorders, like bipolar disorder and severe anxiety. It may be adjunctive therapy with other medications, such as antidepressants, to treat mood disorders. 

perphenazine is sometimes used to manage severe nausea and vomiting, particularly when other medications have been ineffective. It might also be used as an off-label to treat certain conditions, such as agitation and aggression, in patients with dementia. 

As with all medications, perphenazine should be used only under the guidance of physician with experience treating psychiatric disorders. The healthcare professional will carefully consider perphenazine’s potential benefits and risks before prescribing it to a patient.