amitriptyline/perphenazine

Action and Spectrum

Drug Interaction

Adverse Reaction

Black Box Warning

Black Box Warning: 

Antidepressants increase the risk of suicide attempts in young adults and adolescents. 

Psychotic patients with dementia are at higher risk of death. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 
• Glaucoma 
• Urinary retention 
• Severe CNS depression 
• Coma 

Caution 

• Cardiovascular disorders 
• Seizure disorders 
• Renal impairment 
• Liver impairment 
• Elderly population 
• Pregnancy 
• Breastfeeding 

Pregnancy / Lactation

Pregnancy consideration:  

Pregnancy Category: D 

Breastfeeding warnings:  

The drug is secreted in breast milk; hence not recommended for lactating females. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence of risk to the fetus is 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 a human product; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergencies for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. The drug is not for pregnant women. 
• Category N: No data for the drug under this category is available. 

Pharmacology

Pharmacology: 

amitriptyline works by inhibiting the reuptake of serotonin and norepinephrine in the brain. By blocking the reuptake of these neurotransmitters, amitriptyline increases their availability in the synaptic cleft, leading to enhanced neurotransmission and mood stabilization. 

perphenazine exerts its effects by blocking dopamine receptors in the brain. Doing so reduces the activity of dopamine, a neurotransmitter that plays a role in psychosis. 

Pharmacodynamics: 

By blocking the reuptake of these neurotransmitters, amitriptyline increases their availability in the synaptic cleft, leading to enhanced neurotransmission and mood stabilization. It also has anticholinergic and antihistaminic properties. 

perphenazine’s actions help manage symptoms of psychosis, such as hallucinations, delusions, and disorganized thinking, which are associated with conditions like schizophrenia. 

Pharmacokinetics: 

Absorption 

amitriptyline is well absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations typically reached within 2 to 12 hours. 

perphenazine is rapidly absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations achieved within 1 to 2 hours. 

Distribution 

amitriptyline is nicely absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations typically reached within 2 to 12 hours. 

Due to its lipophilic nature, Perphenazine is widely distributed throughout the body, including the brain and other tissues. 

Metabolism 

amitriptyline is well absorbed from the gastrointestinal tract after oral administration, with peak plasma concentrations typically reached within 2 to 12 hours. 

perphenazine undergoes hepatic metabolism, primarily through oxidative processes. The major metabolite is 7-hydroxyperphenazine, which is also pharmacologically active. 

Elimination and Excretion 

The elimination half-life of amitriptyline ranges from 10 to 50 hours. It is primarily eliminated in the urine, with a small fraction excreted in the feces. 

perphenazine undergoes hepatic metabolism, primarily through oxidative processes. The major metabolite is 7-hydroxyperphenazine, which is also pharmacologically active. 

Adminstartion

Administration: 

amitriptyline/perphenazine is typically available as oral tablets, and the dosing and administration instructions should be followed as a healthcare professional prescribes. 

Patient Information Leaflet

Patient information leaflet 

Generic Name:  amitriptyline and perphenazine 

Pronounced: a-mee-TRIP-ti-leen-and-per-FEN-a-zeen 

Why do we use amitriptyline and perphenazine? 

amitriptyline and perphenazine are combined to treat certain psychiatric conditions like major depressive disorder and anxiety.