Doxepin Hydrochloride

Class: Tricyclics and Other Norepinephrine-reuptake Inhibitors
VA Class: CN601
Chemical Name: 1-Propamine, 3-dibenz[b,e]oxepin-11(6H)ylidene-N,N-dimethyl-, hydrochloride
Molecular Formula: C₁₉H₂₁NO HCL
CAS Number: 1229-29-4
Brands: Sinequan

• Suicidality


• 
  

  Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.^{h i} Doxepin is not approved for use in pediatric patients <12 years of age.^{a k l} (See Pediatric Use under Cautions.)

  
  


• 
  

  In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.^{h i}

  
  


• 
  

  Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.^{h i j}

  
  


• 
  

  Appropriately monitor and closely observe all patients who are started on doxepin therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.^{h i j} (See Worsening of Depression and Suicidality Risk and Pediatric Use under Cautions.)

  
  

REMS:

FDA approved a REMS for doxepin to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of doxepin and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Dibenzoxepin-derivative tricyclic antidepressant (TCA).^{a b c k l p}

Uses for Doxepin Hydrochloride

Depressive and Anxiety Disorders

Treatment of depression and/or anxiety in psychoneurotic patients.^{a k l} Psychoneurosis symptoms that respond well to doxepin include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension, and worry.^{a k l}

Treatment of depression and/or anxiety associated with alcoholism.^{a k l} (See Specific Drugs under Interactions.)

Treatment of depression and/or anxiety associated with organic disease; consider possible drug interactions if receiving other drugs concomitantly.^{a k l}

Treatment of psychotic depressive disorders with associated anxiety, including involutional depression and manic-depressive disorders.^{a k l}

Chronic Idiopathic Urticaria

Has been effective in the management of chronic idiopathic urticaria† and may be used as an alternative to antihistamines, which are generally considered first-line therapy in patients with this condition.^{n o v w}

Doxepin Hydrochloride Dosage and Administration

General

Depressive and Anxiety Disorders

• 
  

  Allow at least 2 weeks to elapse between discontinuance of therapy with an MAO inhibitor and initiation of doxepin and vice versa.^{a c k l} Also allow at least 5 weeks to elapse when switching from fluoxetine.^{a c k l}

  
  


• 
  

  Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.^{a h i j k} (See Worsening of Depression and Suicidality Risk under Cautions.)

  
  


• 
  

  Avoid abrupt discontinuance of therapy in patients receiving high dosages for prolonged periods.^{a c k l} To avoid withdrawal reactions, taper dosage gradually.^{a k l} (See Withdrawal of Therapy under Cautions.)

  
  

Administration

Oral Administration

Administer orally in up to 3 divided doses or as a single daily dose (if ≤150 mg); may administer once-daily doses at bedtime to reduce daytime sedation.^{a b k l}

Dilute each dose of oral concentrate with 120 mL of water, whole or skim milk, or orange, grapefruit, tomato, prune, or pineapple juice just prior to administration; solution is physically incompatible with many carbonated beverages.^{a b} Patients on methadone maintenance may mix doxepin oral concentrate and methadone syrup with Gatorade, lemonade, orange juice, sugar water, Tang, or water but not with grape juice.^{a b} Bulk dilution and storage not recommended by manufacturer.^a

Dosage

Available as doxepin hydrochloride; dosage expressed in terms of doxepin.^{a b k l}

Individualize dosage carefully according to individual requirements and response.^{a b k l}

When administered as a single daily dose, the maximum daily dose recommended is 150 mg.^{a k l} Commercially available 150-mg capsules of doxepin are intended for maintenance therapy only and are not recommended for initial therapy.^{a b k}

Pediatric Patients

Depressive and Anxiety Disorders

Oral

Adolescents ≥12 years of age should receive dosage recommended for adults.^{a k l} (See Adults under Dosage.)

Adults

Depressive and Anxiety Disorders

Oral

Patients with illness of mild to moderate severity: Initially, 75 mg daily.^{a b k l} May adjust dosage as necessary based on response.^{a k l} Usual maintenance dosage: 75–150 mg daily.^{a k l}

More seriously ill patients: Higher dosages may be necessary; gradually increase dosage to ≤300 mg daily, if necessary.^{a k l}

Dosages >300 mg daily rarely provide additional therapeutic effect.^{a b k l}

Patients with very mild symptomatology or emotional symptoms associated with organic brain syndrome: Lower dosages may be adequate; some patients respond to 25–50 mg daily.^{a b k l}

Prescribing Limits

Pediatric Patients

Depressive and Anxiety Disorders

Oral

Adolescents ≥12 years of age: Maximum 300 mg daily.^{a b k l}

Adults

Oral

Maximum 300 mg daily.^{a b k l}

Special Populations

Geriatric Patients

Select dosage at the lower end of recommended range since decreased hepatic, renal, or cardiac function and concomitant illness and medications are more frequent; increase dosage more gradually and monitor closely.^{a k l} May administer before bedtime.^a (See Geriatric Use under Cautions.)

Cautions for Doxepin Hydrochloride

Contraindications

• 
  

  Although the manufacturers do not state that doxepin is contraindicated in patients receiving MAO inhibitors, concurrent or recent (i.e., within 2 weeks) therapy with MAO inhibitors generally is contraindicated in patients receiving TCAs. ^{a c k l} (See MAO Inhibitors under Interactions.)

  
  


• 
  

  Glaucoma or urinary retention.^{a k l}

  
  

• 
  

  Known hypersensitivity to doxepin or other dibenzoxepin-derivative TCAs.^{a k l}

  
  

Warnings/Precautions

Warnings

Shares the toxic potentials of other TCAs; observe the usual precautions of TCA therapy.^{a b c k l}

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.^{g h i j} However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.^{h i j}

Appropriately monitor and closely observe patients receiving doxepin for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.^{h i j} (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.^{i j} Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.^{h i j} (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.^{a c d i k l}

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder [OCD]) or nonpsychiatric disorders.ⁱ

Bipolar Disorder

May unmask bipolar disorder.ⁱ (See Activation of Mania or Hypomania under Cautions.) Doxepin is not approved for use in treating bipolar depression.^{k l}

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.^{a i k l}

Sensitivity Reactions

Possible sensitivity reactions including skin rash, photosensitization, edema, and pruritus.^{a k}

General Precautions

Activation of Mania or Hypomania

Possible activation of mania and hypomania, particularly in patients with bipolar disorder; decrease dosage and/or administer an antipsychotic agent concomitantly.^{a c k l} (See Bipolar Disorder under Cautions.)

Cognitive/Physical Impairment

Mental alertness or physical coordination required for performing hazardous tasks (e.g., driving, operating machinery) may be impaired.^{a c k l}

Response to alcohol may be potentiated.^{a c k l}

Anticholinergic Effects

Use with caution in patients for whom excess anticholinergic activity could be harmful (e.g., history of urinary retention, increased IOP).^{a c k l} (See Contraindications under Cautions.)

Withdrawal of Therapy

Possibly severe withdrawal reactions; avoid abrupt discontinuance of therapy and taper dosage gradually.^{a c k l}

Psychosis

Possible exacerbation of psychosis in patients with schizophrenia; decrease dosage or administer an antipsychotic agent concomitantly.^{a c k l}

Specific Populations

Pregnancy

Category C.^e

Lactation

Distributes into milk;^{100 101 a c e k l r s} some clinicians recommend that breast-feeding be avoided during doxepin therapy.^{e r s}

Pediatric Use

Safety of doxepin in pediatric patients <12 years of age has not been established.^{a c k l}

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, OCD, or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).^{a i k} However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.^g No suicides occurred in these pediatric trials.^{a g i k}

Carefully consider these findings when assessing potential benefits and risks of doxepin in a child or adolescent for any clinical use.^{a g h i j k l} (See Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{a k l}

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.^{h i} (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Doxepin generally is well tolerated in geriatric patients.^{a k l} Possible increased sensitivity to anticholinergic (e.g., dry mouth, constipation, vision disturbance), cardiovascular, orthostatic hypotension, and sedative effects of TCAs.^{k l}

Titrate dosage carefully.^{a k l} (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Drowsiness, anticholinergic effects (e.g., dry mouth, constipation, blurred vision), GI effects (e.g., nausea, vomiting, diarrhea).^{a c k l m n o}

Interactions for Doxepin Hydrochloride

Metabolized in the liver by various CYP isoenzymes (e.g., CYP1A2, CYP2D6, CYP3A4).^{a k l}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6: potential pharmacokinetic interaction (increased plasma doxepin concentrations) with concomitant use of CYP2D6 inhibitors; use with caution.^{a k l} Consider doxepin dosage adjustment whenever a CYP2D6 inhibitor is added or discontinued.^{a k l}

Specific Drugs

Drug	Interaction	Comments
Alcohol	Potentiates the effects of alcoholc k l	Avoid concomitant usea k l Increased risks if overdose or suicide attempt occursa k l
Antiarrhythmics: class 1C (e.g., flecainide, propafenone); quinidine	Potential for decreased doxepin metabolisma c k l	Monitor for TCA toxicity; dosage adjustment may be neededa c k l
Anticholinergic agents	Hyperthermia, particularly during hot weather, and paralytic ileus possible c	Use with caution; dosage adjustment may be neededc
Antipsychotics (e.g., phenothiazines)	Potential for decreased doxepin metabolisma c k l	Dosage adjustment may be neededa c k l
Cimetidine	Possible increased plasma doxepin concentrationsa k l t u Potential for tricyclic toxicity, particularly anticholinergic adverse effectsa c k l t u	Monitor for TCA toxicity; dosage adjustment may be neededc u
CNS depressants (e.g., analgesics, antihistamines, barbiturates, general anesthetics, opiates)	Potentiates the effects of CNS depressantsc
Guanethidine and related compounds	Antagonizes the antihypertensive effects of guanethidine and related compounds at doxepin dosages >150 mg daily; at dosages ≤150 mg daily, antagonism of antihypertensive effects not reporteda c k l
Levodopa	May interfere with levodopa absorptionc	Monitor levodopa dosage carefullyc
MAO inhibitors	Potentially life-threatening serotonin syndrome a c k l	Concomitant use with TCAs generally contraindicateda c k l Allow at least 2 weeks to elapse when switching to or from these drugsa c k l
Methylphenidate	Potential for decreased metabolism and increased therapeutic efficacy and toxicity of TCAsc
SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)	Possible serotonin syndromec Potential for decreased doxepin metabolism and increased plasma concentrationsa c k l	Use with caution and monitor for TCA toxicity; dosage adjustment may be neededa c k l Allow at least 5 weeks to elapse when switching from fluoxetinea c k l
Sympathomimetic agents (e.g., amphetamines, epinephrine, isoproterenol, norepinephrine, phenylephrine)	Increased vasopressor and/or cardiac effectsc	Use with caution; dosage adjustment may be requiredc
Thyroid agents	Possible cardiac arrhythmiasc	Use with caution c
Tolazamide	Severe hypoglycemia reported in at least one patienta k l

Doxepin Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from the GI tract following oral administration; bioavailability averages approximately 30%.^{b c m p q}

Peak plasma concentrations usually occur within 2 hours after oral administration.^{b m p q}

Onset

Anxiolytic effect occurs prior to antidepressant effect; antidepressant effect usually occurs within 2–3 weeks.^{a k l}

Distribution

Extent

Doxepin and its active N-demethylated metabolite are distributed into milk in concentrations ranging from about 30–140% and 10–115%, respectively, of those in maternal serum.^{100 101 a c e k l r s} Substantial concentrations of the active metabolite have been detected in the serum and urine of nursing infants whose mothers were receiving 75–150 mg of doxepin daily.^{100 101}

Plasma Protein Binding

Highly bound to plasma protein.^{c p}

Elimination

Metabolism

Extensively metabolized in the liver by various CYP isoenzymes (principally CYP2D6; also CYP1A2, CYP3A4); undergoes demethylation to pharmacologically active metabolite, N-desmethyldoxepin.^{a b k m p q} Poor metabolizers of CYP2D6 metabolize the drug more slowly than normal metabolizers.^{a k l}

Elimination Route

Excreted principally in urine.^c

Half-life

6–24.5 hours.^{b m n p x}

Stability

Storage

Oral

Capsules

Tight, light-resistant containers at 15–30°C.^{b k}

Oral Concentrate

Tight, light-resistant containers at 20–25°C.^{b l}

Actions

• 
  

  Mechanism of action in the management of depressive and anxiety disorders is unknown but may involve inhibition of reuptake of norepinephrine.^{a k l}

  
  

• 
  

  Exhibits anticholinergic, antihistaminic, antiserotonergic, and antiadrenergic activity.^{a c f k l n o}

  
  


• 
  

  Associated with more frequent anticholinergic, sedative, and cardiovascular effects and weight gain than SSRIs.^c

  
  

Advice to Patients

• 
  

  Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.^{a d h i j k l} FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.^{a h i j k l}

  
  


• 
  

  Importance of avoiding certain activities (e.g., operating machinery, driving a motor vehicle) until effects on the individual are known.^{a k l}

  
  


• 
  

  Risk of concomitant use with alcohol.^{a k l}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{a k l}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or planned surgery.^{a k l}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{a k l} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Doxepin Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	10 mg (of doxepin)*	Sinequan (with parabens)	Pfizer
			Doxepin Hydrochloride Capsules	Watson
		25 mg (of doxepin)*	Sinequan (with parabens)	Pfizer
			Doxepin Hydrochloride Capsules	Watson
		50 mg (of doxepin)*	Sinequan (with parabens)	Pfizer
			Doxepin Hydrochloride Capsules	Watson
		75 mg (of doxepin)*	Sinequan (with parabens)	Pfizer
			Doxepin Hydrochloride Capsules	Watson
		100 mg (of doxepin)*	Sinequan (with parabens)	Pfizer
			Doxepin Hydrochloride Capsules	Watson
		150 mg (of doxepin)*	Sinequan (with parabens)	Pfizer
	Solution, concentrate	10 mg (of doxepin) per mL*	Sinequan Oral Concentrate (with parabens)	Pfizer
			Doxepin Hydrochloride Oral Solution (Concentrate) (with parabens)	Teva

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Doxepin HCl 10MG Capsules (MYLAN): 90/$28.99 or 180/$39.97

Doxepin HCl 10MG/ML Concentrate (TEVA PHARMACEUTICALS USA): 120/$23.99 or 360/$49.97

Doxepin HCl 100MG Capsules (MYLAN): 30/$25.99 or 60/$37.97

Doxepin HCl 150MG Capsules (PAR): 30/$25.99 or 90/$55.96

Doxepin HCl 25MG Capsules (PAR): 60/$13.99 or 120/$19.98

Doxepin HCl 50MG Capsules (MYLAN): 60/$24.99 or 180/$52.97

Doxepin HCl 75MG Capsules (MYLAN): 30/$22.99 or 90/$43.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

100. Matheson I, Pande H, Alertsen AR. Respiratory depression caused by N-desmethyldoxepin in breast milk. Lancet. 1985; 2:1124. [IDIS 207267] [PubMed 2865592]

101. Kemp J, Ilett KF, Booth J et al. Excretion of doxepin and N-desmethyldoxepin in human milk. Br J Clin Pharmacol. 1985; 20:497-9. [IDIS 210580] [PubMed 4074620]

102. Pfizer Roerig. Sinequan (doxepin hydrochloride) capsules and oral concentrate prescribing information. New York, NY; 2000 Apr.

103. Food and Drug Administration. Class suicidality labeling language for antidepressants. From the FDA website: ().

104. Food and Drug Administration. Public health advisory: suicidality in children and adolescents being treated with antidepressant medications. Rockville, MD; 2004 Oct 15. From the FDA website: ().

105. Food and Drug Administration. Medication guide: about using antidepressants in children or teenagers. Rockville, MD; 2005 Jan 16. From the FDA website: ().

a. Pfizer Inc. Sinequan(doxepin hydrochloride) capsules and oral concentrate prescribing information. New York, NY; 2005 Jan.

b. AHFS drug information 2007. McEvoy GK, ed. Doxepin hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2373-74.

c. AHFS drug information 2007. McEvoy GK, ed. Tricyclic antidepressant general statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2353-60.

d. American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with major depressive disorder, second edition. From the APA website ().

e. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Baltimore, MD: Williams & Wilkins; 2005:513-16.

f. Neittaanmaki H, Myohanen T, Fraki JE. Comparison of cinnarizine, cyproheptadine, doxepin, and hydroxyzine in treatment of idiopathic cold urticaria: usefulness of doxepin. J Am Acad Dermatol. 1984; 11:483-9. [PubMed 6480953]

g. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007; 297:1683-96. [PubMed 17440145]

h. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site: .

i. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site: .

j. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site:

k. Watson Laboratories, Inc. Doxepin hydrochloride capsule prescribing information. Corona, CA; 2005 May.

l. Teva Pharmaceuticals USA. Doxepin hydrochloride oral concentrate prescribing information. Sellersville, PA; 2005 Jul.

m. Yan JH, Hubbard JW, McKay G et al.. Absolute bioavailability and stereoselective pharmacokinetics of doxepin. Xenobiotica. 2002; 32:615-23. [PubMed 12162857]

n. Greene SL, Reed CE, Schroeter AL. Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria. J Am Acad Dermatol. 1985; 12:669-75. [PubMed 3886724]

o. Goldsobel AB, Rohr AS, Siegel SC et al. Efficacy of doxepin in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. 1986; 78:867-73. [PubMed 3782654]

p. Amsterdam J, Brunswick D, Mendels J. The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. Am J Psychiatry. 1980; 137:653-62. [PubMed 6990798]

q. Rudorfer MV, Potter WZ. Metabolism of tricyclic antidepressants.Cell Mol Neurobiol. 1999; 19:373-409. [PubMed 10319193]

r. Frey OR, Scheidt P, von Brenndorff AI. Adverse effects in a newborn infant breast-fed by a mother treated with doxepin. Ann Pharmacother. 1999; 33:690-3. [PubMed 10410181]

s. Pons G, Rey E, Matheson I et al. Excretion of psychoactive drugs into breast milk: pharmacokinetic principles and recommendations. Clin Pharmacokinet. 1994; 27:270-89. [PubMed 7834964]

t. Sutherland DL, Remillard AJ, Haight KR et al. The influence of cimetidine versus ranitidine on doxepin pharmacokinetics. Eur J Clin Pharmacol. 1987; 32:159-64. [IDIS 229491] [PubMed 3582480]

u. Abernethy DR, Todd EL. The influence of cimetidine versus ranitidine on doxepin pharmacokinetics. Eur J Clin Pharmacol. 1987; 32:159-64. [IDIS 229491] [PubMed 3582480]

v. Ormerod AD. Urticaria: recognition, causes and treatment. Drugs. 1994; 48:717-30. [IDIS 359176] [PubMed 7530629]

w. Pons G, Greene SL, Reed CE, Schroeter AL. Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria. J Am Acad Dermatol. 1985; 12:669-75. [PubMed 3886724]

x. Ziegler VE, Biggs JT, Wylie LT et al. Doxepin kinetics. Clin Pharmacokinet. 1978; 23:573-9.