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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Doxepin may be confused with digoxin, doxapram, doxazosin, Doxidan®, doxycycline
Sinequan® may be confused with saquinavir, Serentil®, Seroquel®, Singulair®
Zonalon® may be confused with Zone-A Forte®
International issues:
Doxal® [Finland] may be confused with Doxil® which is a brand name for doxorubicin in the U.S.
Doxal® [Finland]: Brand name for doxycycline in Austria; brand name for pyridoxine/thiamine in Brazil
Pronunciation
(DOKS e pin)
U.S. Brand Names
Index Terms
Generic Available
Yes: Capsule, solution
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral: Depression
Topical: Short-term (<8 days) management of moderate pruritus in adults with atopic dermatitis or lichen simplex chronicus
Use: Dental
Cream: Treatment of burning mouth syndrome and neuropathic pain
Use: Unlabeled/Investigational
Analgesic for certain chronic and neuropathic pain; anxiety
Restrictions
An FDA-approved medication guide concerning the use of antidepressants in children, adolescents, and young adults must be distributed when dispensing an outpatient prescription (new or refill) where this medication is to be used without direct supervision of a healthcare provider. Medication guides are available at http://www.fda.gov/cder/Offices/ODS/medication_guides.htm. Dispense to parents or guardians of children and adolescents receiving this medication.
Pregnancy Risk Factor
B (cream); C (all other forms)
Pregnancy Considerations
Teratogenic effects were not observed in animal studies; however, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed.
Lactation
Enters breast milk/not recommended (AAP rates “of concern”)
Breast-Feeding Considerations
Generally, it is not recommended to breast-feed if taking antidepressants because of the long half-life, active metabolites, and the potential for side effects in the infant.
Contraindications
Hypersensitivity to doxepin, drugs from similar chemical class, or any component of the formulation; narrow-angle glaucoma; urinary retention; use of MAO inhibitors within 14 days; use in a patient during acute recovery phase of MI
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ?65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Doxepin is approved for treatment of depression in adolescents.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.
• May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Doxepin is not FDA approved for the treatment of bipolar depression.
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is high relative to other antidepressants.
• Orthostatic hypotension: May cause orthostatic hypotension (risk is moderate relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is very high relative to other antidepressants.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk conduction abnormalities with this agent is moderate relative to other antidepressants.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
• Thyroid dysfunction: Use with caution in patients with hyperthyroidism or those receiving thyroid supplementation.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use with caution in the elderly.
Dosage form specific issues:
• Topical: Cream formulation is for external use only (not for ophthalmic, vaginal, or oral use). Do not use occlusive dressings. Use for >8 days may increase risk of contact sensitization. Doxepin is significantly absorbed following topical administration; plasma levels may be similar to those achieved with oral administration.
Other warnings/precautions:
• Discontinuation of therapy: Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
Adverse Reactions
Oral: Frequency not defined.
Cardiovascular: Hyper-/hypotension, tachycardia
Central nervous system: Drowsiness, dizziness, headache, disorientation, ataxia, confusion, seizure
Dermatologic: Alopecia, photosensitivity, rash, pruritus
Endocrine & metabolic: Blood sugar increased/decreased, breast enlargement, galactorrhea, libido increased/decreased, SIADH
Gastrointestinal: Xerostomia, constipation, vomiting, indigestion, anorexia, aphthous stomatitis, nausea, unpleasant taste, weight gain, diarrhea, trouble with gums, lower esophageal sphincter tone decrease may cause GE reflux
Genitourinary: Urinary retention, testicular edema
Hematologic: Agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura
Neuromuscular & skeletal: Weakness, tremor, numbness, paresthesia, extrapyramidal symptoms, tardive dyskinesia
Ocular: Blurred vision
Otic: Tinnitus
Miscellaneous: Diaphoresis (excessive), allergic reactions
Topical:
>10%:
Central nervous system: Drowsiness (22%)
Dermatologic: Stinging/burning (23%)
1% to 10%:
Cardiovascular: Edema: (1%)
Central nervous system: Dizziness (2%), emotional changes (2%)
Gastrointestinal: Xerostomia (10%), taste alteration (2%)
<1%: Contact dermatitis, tongue numbness, anxiety
Metabolism/Transport Effects
Substrate (major) of CYP1A2, 2D6, 3A4
Drug Interactions
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Altretamine: May enhance the orthostatic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Aspirin: Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy
BuPROPion: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Dexmethylphenidate: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
DULoxetine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. Risk X: Avoid combination
Methylphenidate: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
NSAID (COX-2 Inhibitor): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy
NSAID (Nonselective): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Propoxyphene: May enhance the CNS depressant effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
St Johns Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Risk D: Consider therapy modification
Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Terbinafine: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
TraMADol: Tricyclic Antidepressants may enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. Risk C: Monitor therapy
Valproic Acid: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Grapefruit juice may inhibit the metabolism of some TCAs and clinical toxicity may result.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava (may increase risk of serotonin syndrome and/or excessive sedation).
Storage
Protect from light.
Mechanism of Action
Increases the synaptic concentration of serotonin and norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane
Pharmacodynamics/Kinetics
Onset of action: Peak effect: Antidepressant: Usually >2 weeks; Anxiolytic: may occur sooner
Absorption: Following topical application, plasma levels may be similar to those achieved with oral administration
Distribution: Crosses placenta; enters breast milk
Protein binding: 80% to 85%
Metabolism: Hepatic; metabolites include desmethyldoxepin (active)
Half-life elimination: Adults: 6-8 hours
Excretion: Urine
Dosage
Oral: Topical: Burning mouth syndrome (dental use): Cream: Apply 3-4 times daily
Oral (entire daily dose may be given at bedtime):
Depression or anxiety:
Children (unlabeled use): 1-3 mg/kg/day in single or divided doses
Adolescents: Initial: 25-50 mg/day in single or divided doses; gradually increase to 100 mg/day
Adults: Initial: 25-150 mg/day at bedtime or in 2-3 divided doses; may gradually increase up to 300 mg/day; single dose should not exceed 150 mg; select patients may respond to 25-50 mg/day
Elderly: Use a lower dose and adjust gradually
Chronic urticaria, angioedema, nocturnal pruritus: Adults and Elderly: 10-30 mg/day
Dosing adjustment in hepatic impairment: Use a lower dose and adjust gradually
Topical: Pruritus: Adults and Elderly: Apply a thin film 4 times/day with at least 3- to 4-hour interval between applications; not recommended for use >8 days. Note: Low-dose (25-50 mg) oral administration has also been used to treat pruritus, but systemic effects are increased.
Dental Usual Dosing
Treatment of burning mouth syndrome and neuropathic pain: Adults: Oral: Topical: Cream: Apply 3-4 times daily
Administration: Oral
Do not mix oral concentrate with carbonated beverages (physically incompatible).
Administration: Topical
Apply thin film to affected area; use of occlusive dressings is not recommended.
Monitoring Parameters
Monitor blood pressure and pulse rate prior to and during initial therapy; monitor mental status, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased); weight; ECG in older adults; adverse effects may be increased if topical formulation is applied to >10% of body surface area
Reference Range
Proposed therapeutic concentration (doxepin plus desmethyldoxepin): 110-250 ng/mL. Toxic concentration (doxepin plus desmethyldoxepin): >500 ng/mL. Utility of serum level monitoring is controversial.
Test Interactions
Increased glucose
Patient Education
Oral: Take exactly as directed; do not increase dose or frequency. It may take several weeks to achieve desired results. Avoid alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); constipation (increased exercise, fluids, fruit, or fiber may help); urinary retention (void before taking medication); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); altered sexual drive or ability (reversible); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, nervousness, restlessness, insomnia, anxiety, excitation, suicide ideation, headache, agitation, impaired coordination, changes in cognition); muscle cramping, weakness, tremors, or rigidity; chest pain, palpitations, or irregular heartbeat; blurred vision or eye pain; yellowing of skin or eyes; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.
Topical: Use as directed. Apply in thin layer; do not overuse. Report increased skin irritation, worsening of condition or lack of improvement.
Geriatric Considerations
The oral form is the preferred agent when sedation is a desired property. Less potential for anticholinergic effects than amitriptyline and less orthostatic hypotension than imipramine. However, dosing should be approached cautiously, initiated at the low end of the dosage range. The pharmacokinetics of doxepin have not been studied in elderly patients. Data from a clinical trial comparing fluoxetine to tricyclics suggest that fluoxetine is significantly less effective than nortriptyline in hospitalized elderly patients with unipolar major affective disorder, especially those with melancholia and concurrent cardiovascular disease.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation)
Oral: Aphthous stomatitis, unpleasant taste, trouble with gums
Topical: Taste alteration
Long-term treatment with TCAs increases the risk of caries by reducing salivation and salivary buffer capacity.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Doxepin is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution. See Dental Comment.
Dental Comment
Doxepin is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”).
Prolongation of the QT interval is thought to result from delayed ventricular repolarization. The repolarization process within the myocardial cell is due to the efflux of intracellular potassium. The channels associated with this current can be blocked by many drugs and predispose the electrical propagation cycle to torsade de pointes.
Doxepin is considered as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. It is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution.
Mental Health: Comment
Tricyclic antidepressants may be classified as tertiary (amitriptyline, doxepin, clomipramine, imipramine, trimipramine) or secondary amines (nortriptyline, desipramine, protriptyline). The tertiary amines are not recommended to treat depression in the elderly. If a TCA is used in the elderly, it should be a secondary amine. The tertiary amines are commonly used in low dosages for various conditions associated with pain. A 1-week supply at maximum dosage taken as a single ingestion is potentially fatal.
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. Assess results of laboratory tests, therapeutic effectiveness, and adverse reactions at beginning of therapy and periodically with long-term use. Monitor CNS status. Be alert for signs of clinical worsening, suicidal ideation, or other changes in behavior. Taper dosage slowly when discontinuing. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
Sinequan®: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg [DSC]
Cream, as hydrochloride:
Prudoxin™: 5% (45 g) [contains benzyl alcohol]
Zonalon®: 5% (30 g, 45 g) [contains benzyl alcohol]
Solution, oral concentrate, as hydrochloride: 10 mg/mL (120 mL)
Sinequan®: 10 mg/mL (120 mL) [DSC]
Pricing: U.S. (www.drugstore.com)
Capsules (Doxepin HCl)
10 mg (90): $19.00
25 mg (60): $13.99
50 mg (60): $14.99
75 mg (30): $8.99
100 mg (30): $13.99
Capsules (Sinequan)
50 mg (60): $55.84
Concentrate (Doxepin HCl)
10 mg/mL (120): $16.00
Cream (Prudoxin)
5% (45): $95.14
Cream (Zonalon)
5% (30): $116.58
5% (45): $138.60
References
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Galynker II, Rosenthal RN, Perkel C, et al, “Doxepin Withdrawal Mania,” J Clin Psychiatry, 1995, 56(3):122-3.
Jastak JT and Yagiela JA, “Vasoconstrictors and Local Anesthesia: A Review and Rationale for Use,” J Am Dent Assoc, 1983, 107(4):623-30.
Jefferson JW, “Tamoxifen-Associated Reduction in Tricyclic Antidepressant Levels in Blood,” J Clin Psychopharmacol, 1995, 15(3):223-4.
Lakshmanan M, Mion LC, and Frengley JD, “Effective Low-Dose Tricyclic Antidepressant Treatment for Depressed Geriatric Rehabilitation Patients. A Double-Blind Study,” J Am Geriatr Soc, 1986, 34(6):421-6.
Larochelle P, Hamet P, and Enjalbert M, “Responses to Tyramine and Norepinephrine After Imipramine and Trazodone,” Clin Pharmacol Ther, 1979, 26(1):24-30.
Levy HB, Harper CR, and Weinberg WA, “A Practical Approach to Children Failing in School,” Pediatr Clin North Am, 1992, 39(4):895-928.
Mitchell JR, “Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man,” J Clin Invest, 1970, 49(8):1596-604.
Mokhlesi B, Leikin JB, Murray P, et al, “Adult Toxicology in Critical Care: Part II: Specific Poisonings,” Chest, 2003, 123(3):897-922.
Pass SE and Simpson RW, “Discontinuation and Reinstitution of Medications During the Perioperative Period,” Am J Health Syst Pharm, 2004, 61(9):899-912.
Roose SP, Glassman AH, Attia E, et al, “Comparative Efficacy of Selective Serotonin Reuptake Inhibitors and Tricyclics in the Treatment of Melancholia,” Am J Psychiatry, 1994, 151(12):1735-9.
Rundegren J, van Dijken J, Mörnstad H, et al, “Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs,” Swed Dent J, 1985, 9(2):55-64.
Svedmyr N, “The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of the Circulatory Effects of Noradrenaline and Adrenalin® in Man,” Life Sci, 1968, 7(1):77-84.
Tran P, Panacek EA, Rhee KJ, et al, “Is Norepinephrine More Efficacious Than Dopamine in Reversing Hypotension Caused by Cyclic Antidepressant Overdose?” Ann Emerg Med, 1995, 25(1):128-30.
Ware MR, “Tricyclic Antidepressant Overdose: Pharmacology and Treatment,” South Med J, 1987, 80(11):1410-5.
Williams JO, “Respiratory Depression in Tricyclic Overdose,” Br Med J, 1972, 1(800):631.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2008
Content last modified September 2008
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