Duo-Vil

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets are indicated for the treatment of patients with moderate to severe anxiety and/or agitation and depressed mood; patients with depression in whom anxiety and/or agitation are moderate or severe; patients with anxiety and depression associated with chronic physical disease; patients in whom depression and anxiety cannot be clearly differentiated.

Schizophrenic patients who have associated symptoms of depression should be considered for therapy with Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil).

Duo-Vil is in a group of drugs called tricyclic antidepressants. Duo-Vil affects chemicals in the brain that may become unbalanced.

Perphenazine (Duo-Vil) is in a group of drugs called phenothiazines (feen-oh-THYE-a-zeens). Perphenazine (Duo-Vil) affects chemicals in the brain that may become unbalanced and cause anxiety.

The combination of Duo-Vil and Perphenazine (Duo-Vil) is used to treat depression, anxiety, and agitation.

Duo-Vil and Perphenazine (Duo-Vil) may also be used for purposes not listed in this medication guide.

Initial Dosage

In psychoneurotic patients whose anxiety and depression warrant combined therapy, one Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablet (2-25) or one Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) -Forte Tablet (4-25) three or four times a day is recommended.

In elderly patients and adolescents, a lower initial dosage may be needed. The dosage may then be adjusted cautiously to produce an adequate response.

In more severely ill patients with schizophrenia, two Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) -Forte Tablets (4-25) three times a day are recommended as the initial dosage. If necessary, a fourth dose may be given at bedtime. The total daily dosage should not exceed eight tablets of any strength.

Maintenance Dosage

Depending on the condition being treated, the onset of therapeutic response may vary from a few days to a few weeks or even longer. After a satisfactory response is noted, dosage should be reduced to the smallest dose which is effective for relief of the symptoms for which Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets are being administered. A useful maintenance dosage is one Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablet (2-25) or one Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) -Forte Tablet (4-25) two to four times a day. In some patients, maintenance dosage is required for many months.

Duo-Vil 2-10 Tablets (2-10) can be used to increase flexibility in adjusting maintenance dosage to the lowest amount consistent with relief of symptoms.

How supplied

Duo-Vil 2-10 Tablets (Perphenazine (Duo-Vil) 2 mg and Duo-Vil hydrochloride 10 mg): deep yellow, sugar-coated tablets branded in blue-black with the Schering trademark and either product identification letters ANA, or number 287; bottles of 100 (NDC 0085-0287-04) and box of 100 for unit-dose dispensing (10 strips of 10 tablets each) (NDC 0085-0287-08).

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets (Perphenazine (Duo-Vil) 2 mg and Duo-Vil hydrochloride 25 mg): pink, sugar-coated tablets branded in red with the Schering trademark and either product identification letters ANC, or number 598; bottles of 100 (NDC 0085-0598-04) and box of 100 for unit-dose dispensing (10 strips of 10 tablets each) (NDC 0085-0598-08).

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) -Forte Tablets (Perphenazine (Duo-Vil) 4 mg and Duo-Vil hydrochloride 25 mg): red, sugar-coated tablets branded in blue with the Schering trademark and either product identification letters ANE, or number 720; bottles of 100 (NDC 0085-0720-04) and box of 100 for unit-dose dispensing (10 strips of 10 tablets each) (NDC 0085-0720-08).

Store Duo-Vil 2-10, 2-25, 4-25 Tablets between 2° and 25°C (36° and 77°F). In addition, protect unit-dose packages from excessive moisture.

* Poisindex® Toxicologic Management. Topic: Antidepressants, Tricyclic. Micromedex Inc. Vol 85.

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) ®

brand of Perphenazine (Duo-Vil) and

Duo-Vil hydrochloride

Duo-Vil 2-10 TABLETS (2-10), USP

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) TABLETS (2-25), USP

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) -FORTE TABLETS (4-25), USP

Schering Corporation

Kenilworth, NJ 07033 USA

All rights reserved.

See also:
What is the most important information I should know about Duo-Vil?

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets are contraindicated in comatose or greatly obtunded patients and in patients receiving large doses of central nervous system depressants (barbiturates, alcohol, narcotics, analgesics, or antihistamines); in the presence of existing blood dyscrasias, bone marrow depression, or liver damage; and in patients who have shown hypersensitivity to Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets, its components, or related compounds.

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets are also contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic damage, since a hyperthermic reaction with temperatures in excess of 104°F may occur in such patients, sometimes not until 14 to 16 hours after drug administration. Total body ice-packing is recommended for such a reaction; antipyretics may also be useful.

Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets should not be given concomitantly with a monoamine oxidase inhibiting compound. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. In patients who have been receiving a monoamine oxidase inhibitor, it is recommended that 2 weeks or longer elapse before the start of treatment with Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets to permit recovery from the effects of the MAO inhibitor and to avoid possible potentiation. Treatment with Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets should be initiated cautiously in such patients, with gradual increase in dosage until a satisfactory response is obtained.

Duo-Vil hydrochloride is not recommended for use during the acute recovery phase following myocardial infarction.

Use Duo-Vil as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Duo-Vil comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Duo-Vil refilled.
• Take Duo-Vil by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
• Do not suddenly stop taking Duo-Vil. You may have an increased risk of side effects. If you need to stop Duo-Vil, your doctor will gradually lower your dose.
• If you miss a dose of Duo-Vil, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Duo-Vil.

Use: Labeled Indications

Depression and anxiety: Treatment of patients with moderate-to-severe anxiety and/or agitation and depression; schizophrenia with depressive symptoms

Schizophrenia with depressive symptoms: Treatment of patients with schizophrenia with depressive symptoms

See also:
What other drugs will affect Duo-Vil?

Drug Interactions: Drugs Metabolized by P450 2D6 The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7%-10% of Caucasians are so-called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (eight-fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), eg, fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6.

Perphenazine (Duo-Vil)

Patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, reduced amounts of anesthetics or central nervous system depressants may be necessary.

Since phenothiazines and central nervous system depressants (opiates, analgesics, antihistamines, barbiturates) can potentiate each other, less than the usual dosage of the 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 organic phosphate 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 Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets. The risk of suicide and the danger of overdose may be increased in patients who use alcohol excessively due to its potentiation of the drug's effect.

Duo-Vil Hydrochloride

When Duo-Vil hydrochloride is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required.

Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs.

Concurrent use of large doses of ethchlorvynol should be used with caution, since transient delirium has been reported in patients receiving this drug in combination with Duo-Vil hydrochloride.

This drug may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.

Concurrent administration of Duo-Vil hydrochloride and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to patients for whom it is essential.

Discontinue the drug several days before elective surgery, if possible.

Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressant. Serious anticholinergic symptoms (severe dry mouth, urinary retention, blurred vision) have been associated with elevations in the serum levels of the tricyclic antidepressant when cimetidine is added to the drug regimen. Additionally, higher than expected steady-state serum concentrations of the tricyclic antidepressant have been observed when therapy is initiated in patients taking cimetidine.

Alternatively, decreases in the steady-state serum concentration of the tricyclic antidepressant have been reported in well-controlled patients on concurrent therapy upon discontinuance of cimetidine. The therapeutic efficacy of the tricyclic antidepressant may be compromised in these patients as the cimetidine is discontinued.

See also:
What are the possible side effects of Duo-Vil?

Adverse reactions to Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets are the same as those to its components, Perphenazine (Duo-Vil) and Duo-Vil hydrochloride. There have been no reports of effects peculiar to the combination of these components in Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets.

Perphenazine (Duo-Vil)

Not all of the following adverse reactions have been reported with Perphenazine (Duo-Vil); however, pharmacological similarities among various phenothiazine derivatives require that each be considered. With the piperazine group (of which Perphenazine (Duo-Vil) is an example), the extrapyramidal symptoms are more common, and others (eg, 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 (Duo-Vil).

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 pediatric patients. 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 (eg, 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, 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 neuroleptic 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, polyuria, bladder paralysis, nasal congestion, pallor, myosis, mydriasis, blurred vision, glaucoma, perspiration, hypertension, hypotension, and a change in pulse rate occasionally may occur. Significant autonomic effects have been infrequent in patients receiving less than 24 mg Perphenazine (Duo-Vil) 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, false-positive pregnancy tests, hyperglycemia, hypoglycemia, glycosuria, syndrome of inappropriate ADH (antidiuretic hormone) secretion.

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 tranquilizers.

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.

Duo-Vil Hydrochloride

Although activation of latent schizophrenia has been reported with antidepressant drugs, including Duo-Vil hydrochloride, it may be prevented with Duo-Vil (Perphenazine (Duo-Vil) and Duo-Vil) Tablets in some cases because of the antipsychotic effect of Perphenazine (Duo-Vil). A few instances of epileptiform seizures have been reported in chronic schizophrenic patients during treatment with Duo-Vil hydrochloride.

Note: Included in the listing which follows are a few adverse reactions which have not been reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when Duo-Vil hydrochloride is administered.

Allergic Effects: rash, pruritus, urticaria, photosensitization, edema of face and tongue.

Anticholinergic Effects: dry mouth, blurred vision, disturbance of accommodation, constipation, paralytic ileus, urinary retention, dilatation of urinary tract.

Cardiovascular Effects: hypotension, hypertension, tachycardia, palpitations, myocardial infarction, arrhythmias, heart block, stroke.

CNS and Neuromuscular Effects: confusional states; disturbed concentration; disorientation; delusions; hallucinations; excitement; jitteriness; anxiety; restlessness; insomnia; nightmares; numbness, tingling, and paresthesias of the extremities; peripheral neuropathy; incoordination; ataxia; tremors; seizures; alteration in EEG patterns; extrapyramidal symptoms; tinnitus.

Endocrine Effects: testicular swelling and gynecomastia in the male, breast enlargement and galactorrhea in the female, increased or decreased libido, elevation and lowering of blood sugar levels, syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Gastrointestinal Effects: nausea, epigastric distress, heartburn, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, jaundice, parotid swelling, black tongue. Rarely hepatitis has occurred (including altered liver function and jaundice).

Hematological Effects: bone marrow depression, including agranulocytosis, leukopenia, eosinophilia, purpura, thrombocytopenia.

Other Effects: dizziness, weakness, fatigue, headache, weight gain or loss, increased perspiration, urinary frequency, mydriasis, drowsiness, alopecia.

Withdrawal Symptoms: abrupt cessation of treatment after prolonged administration may produce nausea, headache, and malaise. These are not indicative of addiction.

A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.