perphenazine (Rx)

Brand and Other Names:Trilafon
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablets

  • 2mg
  • 4mg
  • 8mg
  • 16mg

Intractable Hiccoughs (Off-label)

8-16 mg PO qDay divided q8-12hr

Maximum: 24 mg

Treatment of Nausea/Vomiting

8-16 mg PO qDay divided q6-12hr

Maximum: 24 mg

Schizophrenia

Hospitalized patients: 8-16mg PO q6-12hr

Hospitalized patients: Not to exceed 64 mg/day divided q6-12hr

Outpatients: 4-8mg PO q8hr; reduce as soon as possible to minimum effective dose

Hepatic Impairment

Dose adjustment not described in manufacturer's labeling

Renal Impairment

Dose adjustment not described in manufacturer's labeling

Dosage Forms & Strengths

tablets

  • 2mg
  • 4mg
  • 8mg
  • 16mg

Intractable Hiccoughs (Off-label)

<12 years

  • Not recommended by manufacturer

>12 years

  • 8-16 mg PO qDay divided q8-12hr Maximum: 24 mg

Schizophrenia

<12 years

  • Not recommended by manufacturer

>12 years

  • Hospitalized patients: 8-16mg PO q6-12hr
  • Hospitalized patients: Not to exceed 64 mg/day divided q6-12hr
  • Outpatients: 4-8mg PO q8hr; reduce as soon as possible to minimum effective dose

Initiate dosing at lower end of the range

Intractable Hiccoughs

8-16 mg PO qDay divided q8-12hr

Maximum: 24 mg

Treatment of Nausea/Vomiting

8-16 mg PO qDay divided q6-12hr

Maximum: 24 mg

Schizophrenia

Hospitalized patients: 8-16mg PO q6-12hr

Hospitalized patients: Not to exceed 64 mg/day divided q6-12hr

Outpatients: 4-8mg PO q8hr; reduce as soon as possible to minimum effective dose

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Interactions

Interaction Checker

and perphenazine

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Akathisia (60%)

            Frequency Not Defined

            Confusion

            Decreased gag reflex

            EPS

            • Akathisia (60%)
            • Dystonia
            • Muscle stiffness
            • Neuroleptic malignant syndrome (infrequent but serious)
            • Parkinsonism
            • Tardive dyskinesia

            Common

            • Anticholinergic effects
            • Sedation
            • Weight gain
            • Oligomenorrhea/amenorrhea
            • Erectile dysfunction

            Less Common

            • Orthostatic hypotension (post-IM inj), tachycardia
            • Anxiety, agitation, cerebral edema, depression, dizziness, euphoria, headache, insomnia, restless, weakness
            • Anorexia, dyspepsia, constipation, ileus
            • Lens opacities (prolonged use)

            Uncommon

            • ECG changes
            • Photosensitivity
            • Pruritis
            • Galactorrhea
            • Ejaculatory disorder
            • Diarrhea
            • Blood dyscrasia

            Rare

            • Seizure
            • Priapism
            • Cholestatic jaundice
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            Warnings

            Black Box Warnings

            Patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature

            This drug is not approved for the treatment of patients with dementia-related psychosis

            Contraindications

            Documented hypersensitivity to phenothiazines

            Coma, severe hypotension, severe CNS depression, concurrency with large amounts of CNS depressants, poorly controlled seizure disorder, subcortical brain damage with or without hypothalamic damage, myelosuppression, liver damage, blood dyscrasias

            Severe cardiovascular disease

            Lactation

            Cautions

            Avoid using in children with suspected Reye's syndrome

            Use caution in prostatic hypertrophy, stenosing PUD, tardive dyskinesia, hypocalcemia, renal/hepatic impairment, patients who have exhibited a severe reaction to insulin or ECT, history of seizures, asthma, respiratory tract infections, cardiovascular disease

            Perphenazine products can lower convulsive threshold in susceptible individuals; they should be used with caution in alcohol withdrawal and in patients with convulsive disorders; if patient is being treated with an anticonvulsant agent, increased dosage of that agent may be required when perphenazine products are used concomitantly

            Should be used with caution in patients with psychiatric depression; possibility of suicide in depressed patients remains during treatment and until significant remission occurs; this type of patient should not have access to large quantities of this drug

            Caution should be observed in giving it to patients who have previously exhibited severe adverse reactions to other phenothiazines some of the untoward actions of perphenazine tend to appear more frequently when high doses are used; patients should be kept under close supervision

            A significant, not otherwise explained, rise in body temperature may suggest individual intolerance to perphenazine, in which case it should be discontinued

            Patients on large doses who are undergoing surgery should be watched carefully for possible hypotensive phenomena; reduced amounts of anesthetics or central nervous system depressants may be necessary

            If abnormalities in hepatic tests occur, phenothiazine treatment should be discontinued

            Renal function in patients on long-term therapy should be monitored; if blood urea nitrogen (BUN) becomes abnormal, treatment should be discontinued

            Use with caution in patients suffering from respiratory impairment due to acute pulmonary infections, or in chronic respiratory disorders such as severe asthma or emphysema

            Gastritis, nausea and vomiting, dizziness, and tremulousness reported following abrupt cessation of high-dose therapy; reports suggest that these symptoms can be reduced by continuing concomitant antiparkinson agents for several weeks after drug is withdrawn

            Possibility of liver damage, corneal and lenticular deposits, and irreversible dyskinesias should be considered when patients are on long-term therapy

            Because photosensitivity has been reported, undue exposure to sun should be avoided during phenothiazine treatment

            Leukopenia and neutropenia

            • Events of leukopenia/neutropenia and agranulocytosis reported
            • Possible risk factors include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia
            • Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count
            • (CBC) monitored frequently during first few months of therapy discontiue at first sign of a decline in WBC in absence of other causative factors
            • Blood counts should be checked periodically; appearance of signs of blood dyscrasias requires discontinuance of drug and institution of appropriate therapy

            Tardive dyskinesia

            • Risk of developing the syndrome and likelihood that it will become irreversible are believed to increase as the duration of treatment and total cumulative dose of antipsychotic drugs administered to the patient increase; however, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses
            • Antipsychotics should be prescribed in manner that is most likely to minimize occurrence of tardive dyskinesia
            • Chronic antipsychotic treatment should generally be reserved for patients who suffer from chronic illness that 1) is known to respond to antipsychotic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate
            • In patients who require chronic treatment, the smallest dose and shortest duration of treatment producing a satisfactory clinical response should be sought; the need for continued treatment should be reassessed periodically
            • If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered; however, some patients may require treatment despite presence of the syndrome

            Neuroleptic malignant syndrome

            • Neuroleptic malignancy syndrome (NMS) may occur; clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias)
            • Management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available
            • There is no general agreement about specific pharmacologic treatment regimens for uncomplicated NMS
            • If a patient requires antipsychotic drug treatment after recovery from NMS, reintroduction of drug therapy should be carefully considered; patient should be carefully monitored; recurrences reported
            • If hypotension develops, epinephrine should not be administered since its action is blocked and partially reversed
            • If a vasopressor is needed, norepinephrine or dopamine may be used
            • Severe, acute hypotension has occurred with use of phenothiazines and is particularly likely to occur in patients with mitral insufficiency or pheochromocytoma
            • Rebound hypertension may occur in pheochromocytoma patients

            Drug interaction overview

            • Since phenothiazines and central nervous system depressants (opiates, analgesics, antihistamines, barbiturates) can potentiate each other, less than usual dosage of added drug is recommended and caution is advised when they are administered concomitantly
            • Use with caution in patients who are receiving atropine or related drugs because of additive anticholinergic effects and also in patients who will be exposed to extreme heat or phosphorus insecticides
            • The use of alcohol should be avoided, since additive effects and hypotension may occur; patients should be cautioned that their response to alcohol may be increased while they are being treated with perphenazine products; risk of suicide and danger of overdose may be increased in patients who use alcohol excessively due to its potentiation of drug’s effect
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            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: avoid

            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.

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            Pharmacology

            Mechanism of Action

            Antipsychotic that blocks postsynaptic mesolimbic dopaminergic receptors in the brain; it has moderate anticholinergic effects, weak to moderate sedative effects, strong extrapyramidal effects, and strong antiemetic activity

            Pharmacokinetics

            Peak Plasma Time: 1-3 hr; 2-4 hr (metabolite)

            Half-Life: 9-12 hr (; 10-19 hr (metabolite)

            Concentration: 984 pg/mL; 509 pg/mL (metabolite)

            Metabolism: Hepatic P450 enzyme CYP2D6

            Metabolites: 7-hydroxyperphenazine

            Enzymes inhibited: CYP2D6

            Excretion: Urine and feces

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.