Side Effects of perphenazine (Trilafon)

Perphenazine (brand name Trilafon is discontinued) is an oral antipsychotic medication used to manage schizophrenia. Perphenazine is one of the older, first-generation antipsychotic medications.

Although the exact mechanism of antipsychotics is unknown, scientists believe they may work by blocking the action of dopamine in the brain. Dopamine is a neurotransmitter nerves use to communicate with one another. Perphenazine is used when patients do not respond to other antipsychotics.

Common side effects of perphenazine include

• extrapyramidal side effects (abnormal muscle contractions, difficulty breathing and swallowing, and neck spasms),
• low blood pressure,
• constipation,
• dry mouth,
• blurred vision,
• seizures,
• dizziness,
• drowsiness,
• urinary retention,
• worsening of glaucoma, and
• increased or decreased blood glucose.

Serious side effects of perphenazine include

• tardive dyskinesia and
• neuroleptic malignant syndrome.

Drug interactions of perphenazine include as procainamide, sotalol, amiodarone, and dofetilide that affect heart rate and rhythm, because it can cause abnormal heart beats.

• Antidepressants such as fluoxetine, sertraline, and tricyclic antidepressants may reduce the breakdown of perphenazine, leading to increased blood levels and side effects of perphenazine.
• Perphenazine should be used with caution with medications that depress the central nervous system and cause sedation or drowsiness, such as alprazolam, clonazepam, zolpidem, codeine, morphine, and alcohol.
• Such combinations can cause excessive sedation, drowsiness, weakness, confusion, speech impairment, and in severe cases coma or death.
• Combining alcohol with perphenazine also increases the risk of low blood pressure.
• Use of perphenazine during pregnancy has not been adequately studied.

Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and withdrawal symptoms after birth. Symptoms reported included

• agitation,
• hypertonia,
• hypotonia,
• tremor,
• somnolence,
• depressed breathing, and
• feeding disorder.

Safe use of perphenazine by nursing mothers has not been established. Consult your doctor before breastfeeding.

Perphenazine causes extrapyramidal side effects such as:

• Abnormal muscle contractions
• Difficulty breathing and swallowing
• Neck spasms

Other side effects include:

• Low blood pressure
• Constipation
• Dry mouth
• Blurred vision
• Seizures
• Dizziness
• Drowsiness
• Urinary retention
• Worsening of glaucoma
• Increased or decreased blood glucose
• Tardive dyskinesia and neuroleptic malignant syndrome can result from perphenazine treatment. These side effects can be severe so patients must seek medical help.

Not all of the following adverse reactions have been reported with this specific drug; however, pharmacological similarities among various phenothiazine derivatives require that each be considered.

With the piperazine group (of which perphenazine (perphenazine) is an example), the extrapyramidal symptoms are more common, and others (e.g., sedative effects, jaundice, and blood dyscrasias) are less frequently seen.

CNS Effects

Extrapyramidal Reactions

opisthotonus, trismus, torticollis, retrocollis, aching and numbness of the limbs, motor restlessness, oculogyric crisis, hyperreflexia, dystonia, including protrusion, discoloration, aching and rounding of the tongue, tonic spasm of the masticatory muscles, tight feeling in the throat, slurred speech, dysphagia, akathisia, dyskinesia, parkinsonism, and ataxia.

Their incidence and severity usually increase with an increase in dosage, but there is considerable individual variation in the tendency to develop such symptoms.

Extrapyramidal symptoms can usually be controlled by the concomitant use of effective antiparkinsonian drugs, such as benztropine mesylate, and/or by reduction in dosage. In some instances, however, these extrapyramidal reactions may persist after discontinuation of treatment with perphenazine (perphenazine).

Persistent Tardive Dyskinesia

As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may appear after drug therapy has been discontinued. Although the risk appears to be greater in elderly patients on high-dose therapy, especially females, it may occur in either sex and in children.

The symptoms are persistent and in some patients appear to be irreversible. The syndrome is characterized by rhythmical, involuntary movements of the tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements).

Sometimes these may be accompanied by involuntary movements of the extremities. There is no known effective treatment for tardive dyskinesia; antiparkinsonism agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear.

Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. It has been reported that fine, vermicular movements of the tongue may be an early sign of the syndrome, and if the medication is stopped at that time the syndrome may not develop.

Other CNS Effects

include cerebral edema; abnormality of cerebrospinal fluid proteins; convulsive seizures, particularly in patients with EEG abnormalities or a history of such disorders; and headaches.

Neuroleptic malignant syndrome has been reported in patients treated with antipsychotic drugs.

Drowsiness may occur, particularly during the first or second week, after which it generally disappears. If troublesome, lower the dosage. Hypnotic effects appear to be minimal, especially in patients who are permitted to remain active.

Adverse behavioral effects include paradoxical exacerbation of psychotic symptoms, catatonic-like states, paranoid reactions, lethargy, paradoxical excitement, restlessness, hyperactivity, nocturnal confusion, bizarre dreams, and insomnia.

Hyperreflexia has been reported in the newborn when a phenothiazine was used during pregnancy.

Autonomic Effects

dry mouth or salivation, nausea, vomiting, diarrhea, anorexia, constipation, obstipation, fecal impaction, urinary retention, frequency or incontinence, bladder paralysis, polyuria, nasal congestion, pallor, myosis, mydriasis, blurred vision, glaucoma, perspiration, hypertension, hypotension, and change in pulse rate occasionally may occur. Significant autonomic effects have been infrequent in patients receiving less than 24 mg perphenazine (perphenazine) daily.

Adynamic ileus occasionally occurs with phenothiazine therapy, and if severe, can result in complications and death. It is of particular concern in psychiatric patients, who may fail to seek treatment of the condition.

Allergic Effects

urticaria, erythema, eczema, exfoliative dermatitis, pruritus, photosensitivity, asthma, fever, anaphylactoid reactions, laryngeal edema, and angioneurotic edema; contact dermatitis in nursing personnel administering the drug; and in extremely rare instances, individual idiosyncrasy or hypersensitivity to phenothiazines has resulted in cerebral edema, circulatory collapse, and death.

Endocrine Effects

lactation, galactorrhea, moderate breast enlargement in females and gynecomastia in males on large doses, disturbances in the menstrual cycle, amenorrhea, changes in libido, inhibition of ejaculation, syndrome of inappropriate ADH (antidiuretic hormone) secretion, false positive pregnancy tests, hyperglycemia, hypoglycemia, glycosuria.

Cardiovascular Effects

postural hypotension, tachycardia (especially with sudden marked increase in dosage), bradycardia, cardiac arrest, faintness, and dizziness. Occasionally the hypotensive effect may produce a shock-like condition. ECG changes, nonspecific (quinidine-like effect) usually reversible, have been observed in some patients receiving phenothiazine antipsychotics.

Sudden death has occasionally been reported in patients who have received phenothiazines. In some cases, the death was apparently due to cardiac arrest; in others, the cause appeared to be asphyxia due to failure of the cough reflex. In some patients, the cause could not be determined nor could it be established that the death was due to the phenothiazine.

Hematological Effects

agranulocytosis, eosinophilia, leukopenia, hemolytic anemia, thrombocytopenic purpura, and pancytopenia. Most cases of agranulocytosis have occurred between the fourth and tenth weeks of therapy. Patients should be watched closely, especially during that period, for the sudden appearance of sore throat or signs of infection. If white blood cell and differential cell counts show significant cellular depression, discontinue the drug and start appropriate therapy. However, a slightly lowered white count is not in itself an indication to discontinue the drug.

Other Effects

Special considerations in long-term therapy include pigmentation of the skin, occurring chiefly in the exposed areas; ocular changes consisting of deposition of fine particulate matter in the cornea and lens, progressing in more severe cases to star-shaped lenticular opacities; epithelial keratopathies; and pigmentary retinopathy.

Also noted: peripheral edema, reversed epinephrine effect, increase in PBI not attributable to an increase in thyroxine, parotid swelling (rare), hyperpyrexia, systemic lupus erythematosus-like syndrome, increases in appetite and weight, polyphagia, photophobia, and muscle weakness.

Liver damage (biliary stasis) may occur. Jaundice may occur, usually between the second and fourth weeks of treatment, and is regarded as a hypersensitivity reaction. Incidence is low. The clinical picture resembles infectious hepatitis but with laboratory features of obstructive jaundice. It is usually reversible; however, chronic jaundice has been reported.

Metabolism of a number of medications, including antipsychotics, antidepressants, β-blockers, and antiarrhythmics, occurs through the cytochrome P450 2D6 isoenzyme (debrisoquine hydroxylase).

Approximately 10% of the Caucasian population has reduced activity of this enzyme, so-called "poor" metabolizers. Among other populations the prevalence is not known.

Poor metabolizers demonstrate higher plasma concentrations of antipsychotic drugs at usual doses, which may correlate with emergence of side effects.

In one study of 45 elderly patients suffering from dementia treated with perphenazine (perphenazine), the 5 patients who were prospectively identified as poor P450 2D6 metabolizers had reported significantly greater side effects during the first 10 days of treatment than the 40 extensive metabolizers, following which the groups tended to converge.

Prospective phenotyping of elderly patients prior to antipsychotic treatment may identify those at risk for adverse events

The concomitant administration of other drugs that inhibit the activity of P450 2D6 may acutely increase plasma concentrations of antipsychotics.

Among these are tricyclic antidepressants and selective serotonin reuptake inhibitors, e.g., fluoxetine, sertraline and paroxetine.

When prescribing these drugs to patients already receiving antipsychotic therapy, close monitoring is essential and dose reduction may become necessary to avoid toxicity. Lower doses than usually prescribed for either the antipsychotic or the other drug may be required.