Comprehensive Dermatologic Drug Therapy

Cover
Comprehensive Dermatologic Drug Therapy
Copyright
Dedication
Contributors
Preface
Acknowledgments
PART I Introduction
1 - Basic Principles of Pharmacology
	1 - Basic Principles of Pharmacology
		Introduction
		Pharmacokinetics—Part I (Tables 1.2 and 1.3)
			Drug Absorption (The Drug has to be Absorbed and Enter Circulation)
			Distribution (The Drug has to Travel to the Site of Intended Action or to a Reservoir)
			Bioavailability (The Drug has to be ‘Available’ at The Site of Intended Action)
		Pharmacodynamics (The Drug Produces the Desired Pharmacologic Effect)
			Definitions (Table 1.4)
			Drug Receptors
			Enzyme Systems Inhibited by Drugs
			Signal Transduction and Transcription Factors
		Pharmacokinetics—Part II
			Metabolism (The Drug Becomes More Hydrophilic to Favor Renal and Biliary Excretion)
			Excretion (The Relatively Hydrophilic Drug Metabolites Must Leave the Body)
		Percutaneous Absorption
			General Principles
			Vehicles
			Tachyphylaxis
			Transdermal Medication Formulations
		Summary
		Bibliography: Important Reviews and Chapters
2 -
Principles for Maximizing the Safety of Dermatologic Drug Therapy
	Introduction
	Anticipation
		Patient Selection
		Patient Education
		Baseline Laboratory and Related Tests
		Concomitant Drug Therapy—Drug Interactions
		Evolving Guidelines—Risk Factors
	Prevention
		Patient Measures to Reduce Risks
		Therapeutic Interventions to Minimize Drug Risk
		Timing of Risk and Medication Errors
	Diagnosis
		Evolving Guidelines for Monitoring
		A Teamwork Approach for Maximizing the Safety of Drug Therapy
		Use of Optimal Diagnostic Tests
		Higher-Risk Scenarios
	Management
		What to do if Problems Arise—Relatively Minor Complications
		What to do if Problems Arise—Potentially Serious Complications
		What to do if Problems Arise—Potentially Serious Complications
	Parting Thoughts
	Bibliography: Important Reviews and Chapters
3 - Polymorphisms: Why Individual Drug Responses Vary
	Introduction
	Evaluating the Patient
	Factors That Influence Medication Effects (Including Adverse Effects)
		Absorption
		Phase I and Phase II Drug Metabolism
	Drug Metabolism—Phase I Reactions
		Cytochrome P-450 Enzyme System Overview
		CYP1A2 Polymorphism
		CYP2B6 Haplotype Variation
		CYP3A4 Variability
		CYP2C9 Polymorphism
		CYP2C19 Polymorphism
		CYP2D6 Polymorphism
		CYP2D6 Testing
		Sources for Additional Information on CYP-Based Interactions
		Dihydropyrimidine Dehydrogenase
	Drug Metabolism—Phase II Reactions
		P-Glycoprotein
		Thiopurine Methyltransferase
		N-Acetyltransferase
		Glucose-6-Phosphate Dehydrogenase
		Glutathione S-Transferase
		Thymidylate Synthase and Other Polymorphisms in the Folate Pathway
	65Tests for Genetic Polymorphisms and Clinical Significance
	Pharmacogenomic Databases
	Conclusions and Future Directions
	Bibliography: Important Reviews and Chapters
	References*
4 - Adherence to Drug Therapy
	Introduction
	Measures of Adherence
	Factors that Influence Adherence Behavior
	Strategies to Improve Adherence Behavior
		The Physician–Patient Relationship
		Choice of Treatments
		Stress Good Initial Adherence
		Achieving Adherence in Special Groups
	Conclusions
	Bibliography: Important Reviews and Chapters
	References*
5 - Medical Decision Making
	Introduction
	Patient Individualization and Prioritization (Box 5.1)
		Principle #1. Not all patients with a given diagnosis are of equal risk for complications
			Principle #5. There is power in being able to say to the patient ‘I do not know
	Medical Decision Making (Box 5.2)
	Causation Determination (Box 5.3)
		Principle #7. Correlation in timing does not establish causation
			Principle #8. Master the causation algorithm to assess risk from drug therapy versus chance occurrence alone
			Principle #9. Avoid common pitfalls of causation determination
			Principle #10. Boxed warnings or ‘Warnings and Precautions’ by the US Food and Drug Administration are generally not a statement...
	Evaluating the Medical Literature (Box 5.4)
		Principle #11. Keep up to date on the medical literature
			Principle #12. Be aware of what medical literature is available on a given therapeutic issue
			Principle #13. There are ways to know a drug is effective without large studies ‘required’ by evidence-based medicine
	Interpretation of Medical Literature (Box 5.5)
		Principle #14. Seek an optimal level of certainty in medical decision making
			Principle #15. Develop interpretive skills with the ‘P-value’ to minimize type I and II errors
			Principle #16. There are several limitations to the P-value
			Principle #17. Gain ‘confidence’ in interpreting 95% confidence intervals for various ratios
			Principle #18. Seek to understand the true level of risk by looking at attributable risk
			Risk Management (Box 5.6)
			Principle #19. When deciding to take on risk while making a medical decision, agreement between the prescribing physician with b...
			Principle #20. The therapeutic efficacy of a treatment must be scrutinized against the safety profile of that treatment modality...
	Prescriber Responsibilities (Box 5.7)
		Principle #21. Be aware of the cost of your chosen treatment to both the patient and the healthcare system
			Principle #22. Suboptimal efficacy and treatment failure are different and must be distinguished
	Longitudinal Patient Care Decisions (Box 5.8)
		Principle #23. Starting treatment before disease diagnosis is appropriate in many instances
			Principle #24. Realize that many variables may be involved when a patient is not improving
			Principle #25. Techniques to maximize the successful withdrawal of an intervention include (1) setting expectations, (2) accessi...
	Decision-Making Realities (Box 5.9)
PART II Important Drug Regulatory Issues
6 - The FDA Drug ApprovalProcess
	6 - The FDA Drug Approval Process
		Introduction
		Federal Legislation for Drug Safety and Efficacy
			Food Drug and Cosmetic Law
			Kefauver–Harris Drug Amendment
			General Testing Required Prior to Marketing
		Phase I to IV Testing
			Phase I Testing
			Phase II Testing
			Phase III Testing
			Pharmacovigilance Process
			Phase IV Studies
			Prescription Drug User Fee Act
		US Food and Drug Administration Advisory Panels
		Off-Label Drug Use
			US Food and Drug Administration Modernization Act
		Generic Drugs
			Systemic Drugs Bioequivalence
			Topical Drug Testing Required
		Special Drug Approval Categories
			Compassionate Use Regulations
			Drug Price Competition and Patent Restoration Act
			Orphan Drug Act
		Related Issues
			Regulation of Over-the-Counter Drugs, Biologics, and Generics
			Regulation of Combination Products and Surgery
			Comparisons of FDA Regulation With Other Countries
			Precision Medicine
			Some Final Thoughts
		Bibliography: Important Reviews
7 - Pharmacovigilance: Verifying that Drugs Remain Safe
	Introduction
	Summary
	Bibliography: Important Reviews and Chapters
	References*
8 - Drugs Taken Off the Market: Important Lessons Learned
	Introduction
	Presentation of Risk–Benefit in Labeling
	Product Label ‘Lifecycle’ Changes
	Risks and Benefits: US Food and Drug Administration Safety Information
	Drug Withdrawal
		General Principles Concerning Drug Withdrawal Decisions
		Medical Principles—Specific Examples
		Medical Principles—General Issues
	Acknowledgement
	Bibliography: Important Reviews and Websites For Supplemental Information
	References
PART III Systemic Drugs for Infectious Diseases
9 - Systemic Antibacterial Agents
	9 - Systemic Antibacterial Agents
		Introduction
		Penicillins
		Cephalosporins
		β-Lactam and β-Lactamase Inhibitor Combinations
		Other Systemic Antibacterials that Inhibit Cell Wall Synthesis
		Macrolides
		Fluoroquinolones
		Tetracyclines
		Rifampin and Other Rifamycins
		Folate Synthesis Inhibitors
		Lincosamides
		Oxazolidinones
		Special Topics
		Bibliography: Important Reviews and Chapters
		References*
10 - Systemic Antifungal Agents
	Introduction
		Pharmacokinetics in Skin
		Pharmacokinetics in Nails
		Pharmacokinetics in Hair
		Mechanism of Action
		Clinical Use
		Contraindications
		Adverse Effects
		Drug Interactions
		Monitoring Guidelines
	Conclusion
	Bibliography: Important Reviews and Chapters
	References*
11 - Systemic Antiviral Agents
	Introduction
	Drugs for Human Herpes Virus Infections
		Acyclovir
			Pharmacology
			Acyclovir (9-2-hydroxyethoxymethyl guanine or acycloguanosine) (ACV), a guanosine analog, is the most well-known and widely used...
			Clinical Use
			Indications for ACV are found in Box 11.1.1,3,5–19 Box 11.2 details various risks of ACV
				US Food and Drug Administration-Approved Indications
					Herpes Simplex Virus Infections. ACV can be administered topically, orally, and intravenously. The oral form is the most widely ...
					Chickenpox. When used to treat first-episode VZV, the recommended adult dose of oral ACV is 800 mg 5 times daily for 7 days and ...
					Herpes Zoster. ACV is used for recurrences of VZV known as HZ (or shingles). Acute HZ requires 800 mg of ACV to be taken 5 times...
				Off-Label Dermatologic Uses
					Other Herpes Simplex Infections. A variety of subsets of HSV can be treated with ACV in a fashion similar to the regimens outlin...
				Adverse Effects. ACV is generally well tolerated regardless of the route of administration. Infrequent adverse effects (AE) with...
				Drug Interactions. ACV is not metabolized by hepatic microsomal (cytochrome P-450 [CYP]) enzymes. ACV is eliminated by active tu...
		Valacyclovir
			Pharmacology
			Q11.5 Valacyclovir (VACV) is an oral prodrug of acyclovir. (Note that the drug is also commonly spelled ‘valaciclovir’ in the li...
			Clinical Use
			Indications for VACV are found in Box 11.1.1,20–31 Box 11.2 details various risks of VACV
				US Food and Drug Administration-Approved Indications
					Herpes Simplex Infections. VACV is indicated for the treatment of both genital and orofacial HSV infections. For first-episode g...
					Herpes Zoster. Q11.6 VACV has an FDA indication for use in HZ. Treatment requires 1000 mg TID for 7 days. VACV has been shown to...
				Off-Label Dermatologic Uses
					Recurrent Erythema Multiforme. Q11.4 There are few reports in the English-language literature on suppressive VACV therapy for re...
					Other Herpes Simplex Infections. A variety of subsets of HSV can be treated with VACV in a fashion similar to the regimens outli...
				Adverse Effects. The reported AE of VACV include nausea and headaches (as in ACV), with incidences usually not significantly dif...
				Drug interactions. Given that VACV and its active form ACV are not metabolized by hepatic microsomal (CYP) enzymes, there is a r...
		Famciclovir
			Pharmacology
			Q11.5 FCV is the oral prodrug of penciclovir (PCV), an acyclic nucleoside (see Fig. 11.1). Like ACV, PCV must be phosphorylated ...
			Clinical Use
			Indications for FCV are found in Box 11.1.1,35–48 Box 11.2 details various risks of FCV
				US Food and Drug Administration-Approved Indications
					Herpes Simplex Infections. FCV is used for treatment of both orofacial and genital HSV. In the treatment of genital HSV, it is u...
					Herpes Zoster. FCV has been shown to be highly effective in the treatment of HZ. The FDA-recommended FCV dose for zoster in immu...
				Off-Label Dermatologic Uses
					Other Herpes Virus Infections. A variety of subsets of HSV can be treated with FCV in a fashion similar to the regimens outlined...
				Adverse Effects. Like ACV, FCV can rarely cause such AE as headache, nausea, or diarrhea. FCV shares with ACV and VACV an excell...
				Drug Interactions. Given that FCV and its active form PCV are not metabolized by hepatic microsomal (CYP) enzymes, there is a re...
		Vaccines for Human Herpes Virus Infections
			Varicella-Zoster Virus Vaccines. The first available vaccine for prevention of a VZV virus infection is a live-attenuated vaccin...
			Herpes Simplex Virus Vaccines. Prophylactic and therapeutic HSV vaccines have been in development for more than 90 years. Vaccin...
		Overview
		Integrase Strand Transfer Inhibitors
		Highlights of Combination Medications
		Human Immunodeficiency Virus Vaccine Development
	Summary
12 - Systemic Antiparasitic Agents
	Ivermectin
		Pharmacology
		Clinical Use
		Clinical Comparisons
	Albendazole
		Pharmacology
		Clinical Use
	Thiabendazole
		Pharmacology
		Clinical Use
	Alternative Agents—Doxycycline As Antiparasitic Agent
	Bibliography: Important Reviews and Chapters
	References*
PART IV Systemic Immunomodulatory Drugs
13 - Systemic Corticosteroids
	13 - Systemic Corticosteroids
		Systemic Corticosteroids
		Pharmacology (Table 13.1)
			Structure
			Absorption and Distribution
			Metabolism and Excretion
			Mechanism of Action
		Clinical Use
			Food and Drug Administation-Approved Indications and Off-Label Dermatologic Uses
			Intramuscular Corticosteroid Administration
			Pulse Intravenous Corticosteroid Administration
			Adverse Effects
			Hypothalamic-Pituitary-Adrenal-Axis Suppression
			Drug Interactions
			Monitoring Guidelines
			Therapeutic Guidelines
			Bibliography: Important Reviews and Chapters
			References*
14 - Methotrexate
	Introduction
	Pharmacology
		Structure
		Absorption and Distribution
		Metabolism and Excretion
		Mechanism of Action
			Effects on Deoxyribonucleic Acid (DNA) Synthesis. Q14.1 MTX competitively and reversibly binds to DHFR within 1 hour, with an af...
			T-cell Effects. Q14.1 The mechanism of action of MTX in psoriasis was originally thought to be caused by the suppression of hype...
			Immunosuppressive Effects. Q14.1 MTX has activity as an immunosuppressive agent. The effect probably occurs because of inhibitio...
			Anti-inflammatory Effects. Q14.1 It has been traditionally taught that both the beneficial effects and the toxicity of MTX were ...
			Folic Acid Effects on Methotrexate Therapy. Q14.3 The use of folic acid as a method of inhibiting MTX-induced GI AE and reducing...
	Clinical use
		Indications
		US Food and Drug Administration-Approved Dermatologic Indications
			Psoriasis. The major clinical use of MTX in dermatology is in the therapy of psoriasis.24 The selection of the patient for the i...
		Off-Label Dermatologic Uses
			Other Proliferative Disorders. MTX has been reported to be useful for several other conditions. Patients with other presumed epi...
			Immunobullous Dermatoses. Diseases of presumed immunologic origin may also respond to MTX. Specifically, bullous diseases, such ...
			Autoimmune Connective Tissue Diseases. Patients with autoimmune connective tissue diseases (collagen vascular diseases), such as...
			Vasculitis and Neutrophilic Dermatoses. Systemic vasculitis,61 including polyarteritis nodosa62 and cutaneous polyarteritis nodo...
			Other Dermatoses. Significant personal experience, and some literature experience, with MTX therapy for recalcitrant atopic derm...
			Summary of ‘Off-Label’ Dermatology Indications. The use of MTX for ‘off-label’ indications for dermatomyositis, BP, localized sc...
		Adverse Effects
			Hepatotoxicity. The potential for hepatotoxicity in a patient treated with long-term MTX is an important consideration.24,90 Hep...
			Pulmonary Toxicity. In rare instances, pulmonary toxicity, such as acute pneumonitis, can occur.112–117 This pulmonary toxicity ...
			Hematologic Effects. Hematologic toxicity, such as pancytopenia, presents the greatest potential for loss of life as a result of...
			Malignancy Induction. Q14.8 With the wider use of MTX in autoimmune connective tissue diseases, a number of patients with lympho...
			Gastrointestinal Effects. Nausea and anorexia are common AE to MTX. Diarrhea, vomiting, and ulcerative stomatitis are less frequ...
			Reproductive Effects. MTX has long been considered a potent teratogen and abortifacient, but it has far less long-term mutagenic...
			Renal Effects. High-dose therapy (i.e., 50–250 mg/m2 intravenously; dosages used only in chemotherapy for malignant disease) may...
			Other Adverse Effects. Other reported AE to MTX include mild alopecia, headaches, fatigue, and dizziness. If these reactions occ...
		Drug Interactions
		Monitoring Guidelines
			General Issues and Risk-Factor Assessment. Before the first dose, a thorough evaluation of the patient should be completed. The ...
			Liver Biopsy. The need for routine liver biopsy before the initiation of therapy has been questioned. Q14.10 In general, the cho...
			Q14.11 There are many situations in which pretreatment liver biopsy may not be necessary. These clinical scenarios include the f...
			Q14.11 There are several other instances in which a pretreatment MTX liver biopsy is necessary, although subsequent point 5 is i...
			Editor’s Note. (SEW) - At our institution and at many others, the Fibroscan has quickly evolved to the primary screening test fo...
			Laboratory Monitoring. The patient should be monitored closely during the initial phases of therapy with frequent CBC (usually w...
		Therapeutic Guidelines
15 - Azathioprine
	Introduction
	Pharmacology
		Absorption and Distribution
		Metabolism and Excretion
		Mechanism of Action
	Clinical Use
		Off-Label Dermatologic uses
		Contraindications
		Adverse Effects (Box 15.3)
		Drug Interactions
	Summary
	Bibliography: Important Reviews and Chapters
	References*
16 - Mycophenolates
	Introduction
	Pharmacology
	Mechanisms of Action
	Clinical Use
	Off-Label Dermatologic Uses
		Psoriasis
	Immunobullous Disease
		Pemphigus
		Other Immunobullous Dermatoses
	Autoimmune Connective Tissue Disease
		Lupus Erythematosus
		Dermatomyositis
		Vasculitis
		Systemic Sclerosis
		Atopic Dermatitis
	Contraindications
	Adverse Effects
		Carcinogenicity
		Gastrointestinal Toxicity
		Hematologic
		Infections
		Pregnancy
		Drug Interactions
		Treatment Guidelines
		Monitoring Guidelines
	Bibliography: Important Reviews and Chapters
	References*
17 - Cyclosporine
	Introduction
		Pharmacology
		Clinical Use
			Monitoring Guidelines
	Summary
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
18 - Phosphodiesterase-4 and Janus Kinase Inhibitors
	Introduction
	Small Molecule Treatments
	Mechanism of Action of Phosphodiesterase 4 Inhibition
	Phosphodiesterase 4 Inhibitor Therapy
		Apremilast
			Clinical Use
		Crisaborole
			Clinical Use
			Pharmacology and Pharmacokinetics
	Janus Kinase Inhibitors
		Mechanism of Action of Janus Kinase Pathway Inhibition
		Janus Kinase Inhibitor Therapy
		Tofacitinib
			Additional Off-Label Uses
			Monitoring
		Ruxolitinib
		Baricitinib
		Other Janus Kinase Inhibitors
	Conclusion
	Bibliography: Important Reviews and Chapters
	References*
19 - Cytotoxic Agents
	Introduction
	Patient Education Issues
	Antimetabolites
		Thioguanine
			Pharmacology (Table 19.2)
			Clinical Use
		Hydroxyurea
			Pharmacology
			Clinical Use
	Alkylating Agents
		Cyclophosphamide
			Pharmacology
			Clinical Use
			Adverse Effects
		Chlorambucil
			Pharmacology
			Clinical Use
			Off-Label Dermatologic Uses
			Adverse Effects
		Melphalan
	Bibliography: Important Reviews and Chapters
	References*
20 - Dapsone
	Introduction
	Pharmacology
		Absorption and Bioavailability
		Metabolism (Fig. 20.2)
		Excretion
		Mechanisms of Action (Table 20.3)
	Clinical Use
		Dermatologic Indications – Consistent Efficacy
		Contraindications
		Adverse Effects—Pharmacologic
		Adverse Effects—Idiosyncratic
		Pregnancy and Lactation
		Drug Interactions
		Monitoring Guidelines
		Therapeutic Guidelines
	Bibliography: Important Reviews and Chapters
	References*
	Web References
21 - Antimalarial Agents
	Introduction
	Pharmacology
		Structure
		Absorption and Bioavailability
		Metabolism and Excretion
		Mechanism of Action
	Clinical Use
		Off-Label Uses
	Other Potential Benefits
		Contraindications (Box 21.2)
		Adverse Effects
	Monitoring Guidelines84–86,125
	Drug Interactions
	Therapeutic Guidelines
		Treatment of PCT
	Bibliography: Important Reviews and Chapters
	References*
22 - Systemic Retinoids
	Introduction and Historical Perspective
	Pharmacology
		Vitamin a Physiology
			Q22.1 Vitamin A cannot be synthesized in vivo by the human body, and so must be acquired through the diet. In mammals, vitamin A...
		Structure
		Absorption and Distribution
		Metabolism and Excretion
			General Aspects. The metabolism of retinoids is mainly via oxidation and chain shortening to biologically inactive, water-solubl...
			Acitretin Re-esterification (Reverse Metabolism). Q22.2 Alcohol indirectly enhances the re-esterification of acitretin to etreti...
		Mechanism of Retinoid Action
			Transport of Retinoids. Physiologically, RA is predominantly in the all-trans form (ATRA). A small fraction is transported as 13...
			Mechanism At the Nuclear Level. Retinoids exert their physiologic effects by binding to receptors present in the nucleus (Table ...
	Clinical Use
		Practical Considerations
			Psoriasis—Retinoids As Monotherapy. After etretinate was removed from the market in 1998, owing to concerns about its long half-...
			Psoriasis—Retinoids in Combination Therapy. Q22.4 Combination therapy with systemic retinoids and phototherapy is more effective...
			Retinoids in Combination with Biologic Agents. Because retinoids are generally not considered to be immunosuppressive, they may ...
			Acne Vulgaris. The only systemic retinoid that is FDA approved for the treatment of acne is isotretinoin. Current FDA guidelines...
			Cutaneous T-Cell Lymphoma—Mycosis Fungoides and Sézary Syndrome. In 1999 the FDA approved bexarotene for the treatment of the cu...
		Off-Label Dermatologic Uses
			Rosacea. Compared with acne, rosacea tends to be a more chronic disease that frequently flares when systemic therapy is disconti...
			Hidradenitis Suppurativa and Dissecting Cellulitis of the Scalp. Only a few reports describe the use of retinoids in hidradeniti...
			Darier Disease. In early studies involving patients with inherited ichthyosiform diseases, patients with Darier disease were als...
			Pityriasis Rubra Pilaris. Retinoid use in pityriasis rubra pilaris (PRP) has been reported.76–79 Goldsmith and colleagues evalua...
			Ichthyosiform Dermatoses. Although both vitamin A and retinoic acid showed some therapeutic benefit in treating keratinizing dis...
			Chemoprevention of Malignancy. Q22.6 Given the ability of retinoids to influence epidermal development and differentiation,87 va...
			Lupus Erythematosus. Both isotretinoin and etretinate have been used successfully by patients with various forms of cutaneous lu...
			Lichen Planus. Both isotretinoin and etretinate 1 mg/kg daily give mediocre results. Although many patients respond within 4 wee...
			Chronic Hand Eczema. Although not currently approved for this indication in the United States, at the time this chapter was writ...
		Adverse Effects
			Teratogenicity—Women Exposed To Retinoids. Teratogenicity is the most important AE of the retinoids. Q22.7 Common retinoid-induc...
			Teratogenicity—Males Exposed To Retinoids. The outcomes of 13 pregnancies in which the father was taking acitretin, at or around...
			The ‘iPledge’ Registry Requirements. Because of concerns about the number of pregnancies that continued to occur, while patients...
			Mucocutaneous Adverse Effects. Dry mucous membranes and skin is a common complaint in patients taking isotretinoin and acitretin...
			Lipid Effects. Q22.8 The most common laboratory abnormality observed in patients taking systemic retinoids is elevation in serum...
			Depression. Psychiatric AE are primarily reported with isotretinoin use; however, the exact nature and cause of these AE are not...
			Inflammatory Bowel Disease. Q22.10 Isotretinoin has also been implicated as a cause of inflammatory bowel disease (IBD), in the ...
			Bone Effects. The potential for retinoid use to cause similar bone effects to what is seen in chronic vitamin A toxicity (diffus...
			Ocular Effects. Blepharoconjunctivitis is defined as a low-grade inflammation of the conjunctiva and lid margins, and has been r...
			Liver Effects. Elevated transaminases have been reported with both acitretin and isotretinoin use. It has been assumed that thes...
			Thyroid Effects. Q22.11 Abnormalities in thyroid function have only been reported for bexarotene and occurred in 80% of patients...
			Central Nervous System Effects. Changes of pseudotumor cerebri, although infrequent, are the most important central nervous syst...
			Muscle Effects. Myalgias are noted in roughly 15% of isotretinoin-treated patients. An increased frequency and severity of these...
			Hair and Nail Effects. The risk of telogen effluvium caused by the systemic retinoids has been reported to vary over a range of ...
			Hematologic Effects. In CTCL studies, up to 43% of patients receiving bexarotene (300 mg/m2 daily) had reversible leukopenia (10...
		Drug Interactions
		Monitoring Guidelines
		Therapeutic Guidelines
PART V Drugs Used in Conjunction with UV or Visible Light
23 - Psoralen Plus Ultraviolet A Photochemotherapyand Other Phototherapy Modalities
	23 - Psoralen Plus Ultraviolet A Photochemotherapy and Other Phototherapy Modalities
		Introduction
			Pharmacology
			Structure
			Absorption
			Bioavailability
			Metabolism
			Excretion
			Photochemistry
			Mechanism of Action
			Clinical Use
			Treatment Procedure
		Narrow-Band Ultraviolet B Phototherapy
			Introduction
			Clinical Use
			Contraindications
			Treatment Protocol
			Protection
			Adverse Effects
		Targeted Phototherapy
			Introduction
			Clinical Use
			Contraindications
			Treatment Protocol
			Protection
			Adverse Effects
		Uva-1 Phototherapy
			Clinical Use
			Contraindications
			Treatment Protocol
			Adverse Effects
		Acknowledgments
		Bibliography: Important Reviews and Chapters
		References*
24 - Extracorporeal Photochemotherapy (Photopheresis)
	Introduction
	Treatment Delivery and Considerations
	Pharmacology
		Cutaneous T-Cell Lymphoma
		Autoimmune Dermatoses
	Clinical Use
		US Food and Drug Administration-Approved Indications
		Other Dermatologic Uses—Treatment of T-Cell-Mediated Autoimmune Dermatoses
		Adverse Effects
		Therapeutic Guidelines
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
25 - Photodynamic Therapy
	Introduction
	Pharmacology
		Structure
		Absorption and Bioavailability
		Metabolism and Elimination
		Mechanisms of Action
		Formulations Available
	Clinical Use
		US Food and Drug Administration-Approved Indications
		Off-Label Uses
		Contraindications
		Precautions
		Adverse Effects
		Drug Interactions
		Monitoring Guidelines
		General Therapeutic Guidelines for Photodynamic Therapy Treatment of Actinic Keratoses
	Bibliography: Important Reviews and Chapters
	References*
PART VI Biologic Therapeutics
26 - Tumor Necrosis FactorInhibitors
	26 - Tumor Necrosis Factor Inhibitors
		Introduction—Psoriasis Pathogenesis
		Etanercept
			Pharmacology
			Clinical Use
		Infliximab
			Pharmacology
			Clinical Use
				Off-Label Dermatologic Uses
		Adalimumab
			Pharmacology
			Clinical Use
		Certolizumab Pegol
			Pharmacology
			Clinical Use
		Tumor Necrosis Factor–Inhibitor Use for Psoriatic Arthritis
		Adverse Effects of the TNFi In General
		Bibliography: Important Reviews and Chapters
		References*
27 - Interleukin 12/23 Inhibitors
	Introduction
	Monoclonal Antibody Treatments
	Interleukin-12/23 Therapy - Ustekinumab
		US Food and Drug Administration Approval
		Ustekinumab
			Clinical Use—Ustekinumab
			Adverse Effects
		Overview of Adverse Effects—Interleukin Inhibitors
	Conclusions
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
28 - Interleukin 17 Inhibitors
	Introduction
	Secukinumab
		Dermatologic Indications and Dosages
		Pharmacology
		Clinical Use: Plaque Psoriasis
		Clinical Use: Psoriatic Arthritis
		Off-Label/Other Dermatologic Uses
		Safety and Monitoring
	Ixekizumab
		Dermatologic Indications and Dosages
		Pharmacology
		Clinical Use: Plaque Psoriasis
		Clinical Use: Psoriatic Arthritis
		Off-Label/Other Dermatologic Uses
	Brodalumab
		Dermatologic Indications and Dosages
		Pharmacology
		Clinical Use: Plaque Psoriasis
		Off-Label/Other Dermatologic Uses
		Safety and Monitoring Guidelines
	Common Adverse Events Among All IL-17 Inhibitors
		Infections
		Candidiasis
		Neutropenia
		Inflammatory Bowel Disease
		Latent Tuberculosis Infection
		Live Vaccinations
	Summary
	Bibliography: Important Reviews and Chapters
	References*
29 - Interleukin 23 Inhibitors
	Introduction
	US Food and Drug Administration Approval
	Guselkumab
		Pharmacology
		Clinical Use
			Adverse Effects
	Tildrakizumab
		Pharmacology
		Clinical Use
			Adverse Effects
	Risankizumab
		Pharmacology
			Clinical Use
			Adverse Effects
	Future IL-23 Inhibitors for Psoriasis
	Conclusion
	Bibliography: Important Reviews and Chapters
	References*
30 - Rituximab
	Introduction
		Rituximab
			Pharmacology
			Clinical Use
	Bibliography: Important Reviews and Chapters
	References*
31 - Additional Biologic Therapeutics: Dupilumab, Omalizumab, Others
	Dupilumab
		Pharmacology
			Structure. Dupilumab is a recombinant, fully human IgG4κ mAb targeted against the α-subunit of IL-4 receptors (type 1 and type 2...
			Pharmacokinetics. Dupilumab demonstrates nonlinear pharmacokinetic behavior. Systemic exposure to dupilumab increases more than ...
			Mechanism of Action. Q31.4 Dupilumab directly antagonizes the α-subunit of both type 1 and type 2 IL-4 receptors. Type 1 recepto...
		Clinical Use
			US Food And Drug Administration-Approved Dermatology Indication (Box 31.1). Dupilumab has been FDA-approved for the treatment of...
			Off-Label Dermatologic Indications. Q31.5 Dupilumab was developed and investigated as a targeted therapy for AD. Clinicians are ...
				Alopecia Areata. Clinical reports of dupilumab use and alopecia areata are both conflicting and limited. One case report of conc...
				Idiopathic Chronic Eczematous Eruption of Aging. Dupilumab has been used in one case of idiopathic chronic eczematous eruption o...
				Pemphigus Vulgaris and Pemphigus Foliaceus. Similar to the Th2 dominance seen in AD, pemphigus vulgaris (PV) and pemphigus folia...
				Contraindications. Dupilumab is contraindicated in patients with a known hypersensitivity to the drug or any of its components.1...
			Warnings and Precautions
				General Considerations. Administration of live vaccinations should be avoided in patients on dupilumab. Administration of limite...
				Hypersensitivity. Hypersensitivity reactions to dupilumab are rare, reported in less than 1% of drug-receiving subjects in clini...
				Special Populations. Dupilumab has not been studied in human pregnancy. Endogenous IgG transfers from mother to fetus across the...
			Adverse Effects. The most common AE with dupilumab are injection site reactions, conjunctivitis, oral herpes, blepharitis, dry e...
				Injection Site Reaction. Q31.6 Injection site reaction is the most common AE with dupilumab. Incidence in trials was 13.2% with ...
				Conjunctivitis and Keratitis. Meta-analysis of AE from four clinical trials (CHRONOS, SOLO1, SOLO2, and a phase IIb trial) revea...
			Drug Interactions. During states of chronic inflammation, increased cytokine levels (including IL-4 and IL-13) can affect cytoch...
			Monitoring Guidelines. There are no recommended monitoring guidelines for dupilumab
	Omalizumab
		Pharmacology
			Structure. Omalizumab is a recombinant humanized IgG1κ mAb directed against free human IgE with a molecular weight of 149kDa (Ta...
			Pharmacokinetics. The pharmacokinetics of omalizumab follow a first-order absorption model and become linear with dosages greate...
			Mechanism of Action. Q31.8 Omalizumab selectively binds free IgE with high affinity at the Cε3 domain on the heavy chain, at the...
			Q31.9 The most well understood and agreed upon mechanisms for omalizumab in CIU are summarized here
		Clinical Use
			US Food and Drug Administration-Approved Indications (Box 31.3). Omalizumab is FDA-approved for patients 6 years and older with ...
			Off-Label Dermatologic Indications
				Atopic Dermatitis. The efficacy of omalizumab in AD has been a topic of debate, with numerous conflicting case reports and serie...
				Bullous Pemphigoid. Bullous pemphigoid (BP) is characterized by IgG autoantibodies directed against hemidesmisomal proteins bull...
				Latex Allergy. Latex allergy is a type I hypersensitivity reaction mediated by IgE that is commonly seen in occupational setting...
				Food Allergy. As previously mentioned, studies with omalizumab have shown that IgE FcεRI receptor suppression is separated tempo...
				Other Possible Uses. There have been numerous reports of omalizumab used to treat several other dermatologic conditions off-labe...
			Contraindications. Omalizumab is contraindicated in patients who have a known severe hypersensitivity to the drug or any of its ...
			Warnings and Precautions
				Anaphylaxis. Q31.10 Omalizumab carries a Boxed Warning for the risk of anaphylaxis. Symptoms of anaphylaxis with omalizumab incl...
					Malignancy. Initial phase I to III clinical trials with omalizumab demonstrated a slightly increased incidence of malignancy (0....
				Special Populations. Omalizumab is traditional pregnancy category B. As an IgG antibody, omalizumab is able to cross the placent...
				Helminth (Parasite) Infection. A 1-year trial of patients at increased risk for helminth infections in Brazil found that 50% (34...
			Adverse Effects. Initial phase III CIU trials reported similar incidences of AE between omalizumab and control groups.80,81,83 H...
			Monitoring Guidelines. Clinicians should monitor patients for an appropriate period of time after omalizumab administration for ...
	Other Biologic Therapies in Development
PART VII Miscellaneous Systemic Drugs
32 - Antihistamines
	32 - Antihistamines
		Historical Overview
			First-Generation H1 Antihistamines
			Second-Generation H1 Antihistamines
			The Mast Cell, its Mediators and Stimuli
			Histamine Receptors and Resultant Effects
			Antihistamine Mechanism of Action
		First-Generation Antihistamines
		Second-Generation H1 Antihistamines
			Fexofenadine
			Loratadine
			Cetirizine
			Desloratadine
			Levocetirizine
		H1 Antihistamine in Pregnancy and Lactation
		H2 Antihistamines
		Tolerance (Tachyphylaxis and Subsensitivity)
		Oral and Topical Doxepin
		Antihistamines for Atopic Dermatitis
		Acknowledgment
		Bibliography: Important Reviews and Chapters
		References*
33 - Vasoactive and Antiplatelet Agents
	Pathophysiology Involving Cutaneous Vasculature
	Calcium Channel Blockers
		Pharmacology
		Clinical Use
	β-Blockers
		Pharmacology
		Clinical Use
	Aspirin
		Pharmacology
		Clinical Use
	Dipyridamole (Box 33.4)
		Pharmacology
		Clinical Use
	Pentoxifylline (Box 33.5)
		Pharmacology
		Clinical Use
	Nitric Oxide Donors
	Phosphodiesterase-5 Inhibitors
	Iloprost
	Antiangiogenesis Agents
		Psoriasis
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
34 - Antiandrogens and Androgen Inhibitors
	Introduction
	Physiologic Role of Androgens
		Males
		Females
		Mechanism of Action
	Antiandrogens
		Spironolactone
			Pharmacology
			Clinical Use
		Progestins
		Cimetidine
		Flutamide
		Experimental Therapies
	Androgen Inhibitors
		Finasteride
			Pharmacology
			Clinical Use
			Topical Finasteride
			Adverse Effects
			Drug Interactions
			Monitoring Guidelines
		Dutasteride
			Pharmacology
			Clinical Use
			Off-Label Use
			Adverse Effects
		Ketoconazole
			Pharmacology
	Hormone Preparations
		Oral Contraceptives, Transdermals/Gels, Injectables, Intrauterine Devices
			Pharmacology
		Clinical Use
			Adverse Effects
	Gonadotropin-Releasing Hormone Analogs
	Herbal and Experimental Therapies
		Saw Palmetto, Green Tea, Pygeum, Stinging Nettle, and Others
	Bibliography: Important Reviews and Chapters
	References*
	Web References
35 - Psychotropic Agents
	Introduction
	Classification of Psychodermatologic Disorders
		Categories of Psychodermatologic Disorders
		General Principles in Management of the Above Categories
		Four Major Underlying Psychopathologic Conditions
	The Management of Anxiety in Dermatology
		General Principles
		Specific Medications
			Acute Anxiety
			Chronic Anxiety
		The Management of Depression in Dermatology
			General Principles
			Specific Medications
			Alternatives to Selective Serotonin Reuptake Inhibitor Antidepressants
		The Management of Delusional Disorders in Dermatology
			General Principles
			Specific Medications—Pimozide
		The Management of Obsessive–Compulsive Disorder in Dermatology
			General Principles
			Specific Antidepressants for Obsessive–Compulsive Disorder
			Selective Serotonin Reuptake Inhibitor Antidepressant Choice—Principles Involved
		Psychotropic Medications for Purely Dermatologic Conditions
			Doxepin
			Amitriptyline
			Other Tricyclic Antidepressants
	Summary
	Bibliography: Important Reviews and Chapters
	References*
36 - Intravenous Immunoglobulin Therapy
	Introduction
		Pharmacology
		Mechanism of Action
		Clinical Use
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
37 - Systemic Anticancer Agents: Dermatologic Indications and Adverse Events
	Introduction
	Epidermal Growth Factor Receptor Inhibitors
	Multitargeted Kinase Inhibitors
		Sorafenib
		Imatinib Mesylate
		Nilotinib
	Alkylating Agents
		Carboplatin
		Cisplatin
		Dacarbazine
	Topoisomerase Inhibitors
		Etoposide
	Antimicrotubule Agents (Taxanes)
		Paclitaxel
		Docetaxel
	Anthracyclines
		Doxorubicin Hydrochloride Liposome (Pegylated Liposomal Doxorubicin)
	Histone Deacetylase Inhibitors
		Romidepsin
		Vorinostat
	Miscellaneous
		Denileukin Diftitox
	Monoclonal Antibodies
		Alemtuzumab
	Antimetabolites
		Gemcitabine
		Pralatrexate
		Capecitabine
	Biotherapy (Immunokines)
		Ipilimumab
	PD-1 Inhibitors
		Pembrolizumab
		Nivolumab
		Cemiplimab
	Braf Inhibitors
		Vemurafenib
	Summary
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
38 - Hedgehog Pathway Inhibitors
	Introduction
	Pharmacology
		Structure
		Absorption and Distribution
		Metabolism and Excretion
	Clinical Use
		Us Food and Drug Aministration-Approved Indications
	Off-Label Dermatologic Uses
		Nevoid Basal Cell Carcinoma Syndrome
		Neoadjuvant Use Before Surgery
		Lymphoma
		Graft-Versus-Host Disease
		Systemic Sclerosis
		Melanoma
		Neurofibromatosis
		Other Possible Dermatologic Uses
	Adverse Effects
		Teratogenicity
		Effects on Breastfeeding and Menses
		Overview of Other Adverse Effects
		Effects on Hair Growth
		Taste Disturbances
		Cutaneous Malignancy Risk
		Treatment Resistance
		Pediatric and Geriatric Risk
	Drug Interactions
	Monitoring Guidelines
	Other Hedgehog Inhibitors
	Bibliography: Important Reviews and Chapters
	References*
39 - Drugs for the Skinternist
	Introduction
		Bisphosphonates
			Pharmacology
			Clinical Use
				Adverse Effects
	Bexarotene for Cutaneous T-Cell Lymphoma—Central Hypothyroidism
		Thyroid Replacement Therapy
			Pharmacology
			Clinical Use
				Adverse Effects
	Therapy for Retinoid- or Cyclosporine-Induced Hyperlipidemia
		Lipoprotein Physiology and Pathophysiology
		Statins (HMG-COA Reductase Inhibitors)
			Pharmacology
			Clinical Use
	Fibric Acid Derivatives
		Fenofibrate and Gemfibrozil
			Pharmacology
			Clinical Use
				Adverse Effects
		Ezetimibe
	Vitamin D Therapy
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
40 - Miscellaneous Systemic Drugs
	Introduction
	Anticholinergic Agents—Glycopyrrolate and Oxybutynin
	Attenuated Androgens—Danazol
		Pharmacology
		Clinical use
			Off-Label Dermatologic Uses
	Biotin
	Clofazimine
		Pharmacology
			Mechanism of Action
		Clinical use
			Off-Label Dermatologic Uses
			Adverse Effects
	Colchicine
		Pharmacology
		Clinical Use
			Off-Label Dermatologic Uses
	Fumaric Acid Esters
	Niacinamide
		Pharmacology
		Clinical Use
	Nonsteroidal Anti-inflammatory Drugs
		Pharmacology
		Clinical Use
	Penicillamine
		Pharmacology
		Clinical Use
			Adverse Effects
	Potassium Iodide
		Pharmacology
		Clinical Use
			Off-Label Dermatologic Uses
	Thalidomide
		Pharmacology
		Clinical Use
			Us Food and Drug Administration-Approved Indication
			Off-Label Dermatologic Uses—Well-Documented Benefits
			Adverse Effects
			Monitoring Guidelines
	Vitamin E
	Zinc Sulfate
		Gabapentin and Pregabalin
			Off-Label Uses
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
PART VIII  Topical Drugs for Infectious Diseases
41 - Topical Antibacterial Agents
	Introduction
	Drugs Used for Wound Care and Minor Topical Bacterial Infections
		Bacitracin
			Pharmacology
			Clinical Use
		Polymyxin B
			Pharmacology
			Clinical Use
		Neomycin
			Pharmacology
			Clinical Use
		Mupirocin
			Pharmacology
			Clinical Use
		Retapamulin
			Pharmacology
			Clinical Use
		Ozenoxacin
			Pharmacology
			Clinical Use
		Gentamicin
		Silver Sulfadiazine
		Iodoquinol
	Drugs Used for Acne and Rosacea
		Topical Antibacterial Resistance
		Benzoyl Peroxide
			Clinical Use
		Clindamycin
			Pharmacology
			Clinical Use
		Erythromycin
			Pharmacology
			Clinical Use
		Metronidazole
			Pharmacology
			Clinical Use
		Azelaic Acid
			Pharmacology
			Clinical Use
		Dapsone
			Pharmacology
			Clinical Use
		Sodium Sulfacetamide
	Antiseptics
		Triclosan
		Chlorhexidine
		Povidone-Iodine
		References*
42 - Topical Antifungal Agents
	Introduction
	Polyenes
		Nystatin
			Pharmacology
			Clinical Use
	Azoles
		Miconazole
			Pharmacology
			Clinical Use
		Clotrimazole
			Pharmacology
			Clinical Use
		Ketoconazole
			Pharmacology
			Clinical Use
		Oxiconazole
			Pharmacology
			Clinical Use
		Econazole
			Pharmacology
			Clinical Use
		Sulconazole
			Pharmacology
			Clinical Use
		Sertaconazole
			Pharmacology
			Clinical Use
		Luliconazole
			Pharmacology
			Clinical Use
		Efinaconazole
			Pharmacology
			Clinical Use
	Allylamines and Benzylamines
		Naftifine
			Pharmacology
			Clinical Use
		Terbinafine
			Pharmacology
			Clinical Use
		Butenafine
			Pharmacology
			Clinical Use
	Other Topical Antifungals
		Ciclopirox Olamine
			Pharmacology
			Clinical Use
		Selenium Sulfide
		Tavaborole
			Pharmacology
			Clinical Use
	Comparative Studies
		Dermatophytes
		Candidiasis
		Special Properties
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
43 - Topical and Intralesional Antiviral Agents
	Introduction
	Viricidal Drugs
		Acyclovir
			Pharmacology
			Clinical Use
		Penciclovir
			Pharmacology
			Clinical Use
		Cidofovir
			Pharmacology
			Clinical Use
		Foscarnet
		Idoxuridine
	Immune-Enhancing Drugs
		Imiquimod
			Pharmacology
			Clinical Use
				Off-Label Dermatologic Uses
		Quadrivalent Human Papillomavirus Vaccine
			Verruca Vulgaris (Off Label)
			Mechanism of Action
			Clinical Use
		Interferon-α
		Intralesional Immunotherapy
			Mechanism of Action
			Adverse Effects
			Clinical Use
	Cytodestructive Drugs
		Bleomycin
			Pharmacology
			Clinical Use
		Potassium Hydroxide
			Mechanism of Action
			Clinical Use
		Hydrogen Peroxide
			Mechanism of Action
			Clinical Use
		Podophyllin and Podofilox
			Pharmacology
			Clinical Use
		Trichloroacetic Acid
			Clinical Use
		Cantharidin
			Clinical Use
		Salicylic Acid
		5-Fluorouracil
			Mechanism of Action
			Contraindications and Adverse Effects
			Clinical Use
				Off-Label Dermatologic Use
		Sinecathechin
			Mechanism of Action
			Contraindications and Adverse Events
			Clinical Use
				Off-Label Dermatologic Use
	Bibliography: Important Reviews and Chapters
	References*
44 - Topical Antiparasitic Agents
	Introduction
	Permethrin and Pyrethrins
		Pharmacology
			Mechanism of Action. Q44.1 Pyrethrin and pyrethroids inhibit closure of voltage-gated sodium channels, thereby inhibiting nerve ...
				Resistance. Permethrins preferentially bind to voltage-gated sodium channels at a site away from the pore when it is in an open ...
			Clinical Use
				Indications
					Scabies. Q44.2 Multiple compiled trials comparing permethrin 5% cream or lotion, topical ivermectin 1% lotion, and oral ivermect...
					Pediculosis. Pyrethrins with piperonyl butoxide (Rid, A-200, Proto, R & C shampoo, End Lice) and permethrin 1% cream rinse (Nix)...
				Permethrin 5% cream (Elimite) can also be used in the treatment of head and pubic lice, particularly when resistance to the 1% c...
			Adverse Effects. There have been no reported adverse effects (AE) other than local irritation, which is common to all topical ap...
			Pregnancy and Lactation Prescribing Status. These medications are thought to be safe to use in pregnancy and in breastfeeding wo...
				It is not known whether permethrin is secreted in human milk; however, the manufacturers suggest that nursing should be disconti...
	Ivermectin—Topical (Table 44.3)
		Pharmacology
			Clinical Use
				Indications
					Scabies. Topical ivermectin is not FDA-approved for the treatment of scabies. However, a 2018 Cochrane review comparing the effe...
				Pediculosis. In 2012 the FDA approved ivermectin 0.5% lotion (Sklice) to treat pediculosis in individuals older than 6 months. I...
			Adverse Effects. No serious systemic or toxic AE have been reported with topical ivermectin. The most common reactions are skin ...
			Pregnancy and Lactation Prescribing Status. Because there is minimal systemic absorption, topical ivermectin lotion is thought t...
	Malathion (Table 44.4)
		Pharmacology
			Clinical Use
				Indications
					Pediculosis. Malathion 0.5% lotion (Ovide) is one of the most effective agents for treating pediculosis capitis in the United St...
			Adverse Effects. No serious systemic AE have been reported with the topical application of malathion.17 Additionally, no signifi...
			Pregnancy and Lactation Prescribing Status. Based on limited human data, malathion is not teratogenic and may be used in pregnan...
			Clinical Comparisons. Q44.6 Numerous studies have proven that malathion has superior pediculicidal and ovicidal activity compare...
	Spinosad (Table 44.5)
		Pharmacology
			Indications
			Pregnancy and Lactation Prescribing Status
	Crotamiton
	Benzyl Benzoate
	Precipitated Sulfur
	Lindane
	Melaleuca Alternifolia (Tea Tree) Oil
	Nonpharmacologic Therapy for Head Lice
	Miscellaneous Antiparasitic Agents
		Albendazole
			Pharmacology
				Mechanism of Action. Q44.10 The medication works through binding the colchicine-sensitive cells of tubulin in the intestinal cel...
			Clinical Use
				Indications—Cutaneous Larva Migrans. Cryotherapy was once used as a primary treatment modality; however, this proved to be ineff...
			Adverse Effects. When albendazole is used topically, AE are limited to local irritation and skin ulceration.41
			Drug Interactions. There are no known drug interactions when albendazole is used topically
			Pregnancy and Lactation Prescribing Status. The pregnancy prescribing safety information states that oral albendazole should be ...
	Bibliography: Important Reviews and Chapters
	References*
IX Topical Immunomodulatory Drugs
45 -

Topical Corticosteroids
	45 - Topical Corticosteroids
		Introduction
		Pharmacology
			Estimating Topical Corticosteroid Potency
			Pharmacokinetics
				Mechanism of Action
		Clinical Use
			Indications
			Adverse Effects—Systemic
			Adverse Effects—Local
			Therapeutic Guidelines
		Acknowledgment
		Bibliography: Important Reviews and Chapters
		References*
46 - Topical Retinoids
	Introduction
	Pharmacology
		Structure
		Mechanism of Action
		Teratogenicity
		All-Trans Retinol and All-Trans Retinoic Acid
		Adapalene
		Tazarotene
		Bexarotene
		Alitretinoin (9-Cis Retinoic Acid)
	Clinical Use
		Indications
		Cosmeceuticals
		Adverse Effects
	Acknowledgment
	Bibliography: Important Chapters and Reviews
	References*
47 - Topical and Intralesional Chemotherapeutic Agents
	Introduction
	Topical Chemotherapeutic Agents
		5-Fluorouracil
			Pharmacology
			Clinical Use
		Mechlorethamine/Nitrogen Mustard
			Pharmacology
			Clinical Use
				Adverse Effects
				Therapeutic Guidelines
		Carmustine/Bischlorethylnitrosourea
			Pharmacology
			Clinical Use
				Therapeutic Guidelines
	Intralesional Chemotherapeutic Agents
		Vinblastine
			Pharmacology
			Clinical Use
		Vincristine
			Pharmacology
			Clinical Use
		Bleomycin
			Pharmacology
			Clinical Use
	Bibliography: Important Reviews and Chapters
	References*
48 - Topical Calcineurin Inhibitors
	Introduction
	Tacrolimus
		Pharmacology
		Clinical Use
	Pimecrolimus
		Pharmacology
		Clinical Use
	Acknowledgment
	References*
49 - Topical Vitamin D3
	Introduction
	Pharmacology
		Structure and Biosynthesis
		Metabolism
		Mechanism of Action
	Vitamin D Analogs
		Calcipotriene
		Calcitriol
		Tacalcitol
		Other Vitamin D Analogs
	Calcipotriene—Clinical Use
		US Food and Drug Administration-Approved Indication—Psoriasis
			Plaque Psoriasis. Calcipotriene is approved for the treatment of plaque-type psoriasis in adults. Early studies were all short t...
			Intertriginous Psoriasis. In an open and uncontrolled study, patients with psoriasis in the axillary, inguinal, and anal regions...
			Scalp Psoriasis. In a multicenter prospective observational cohort study, patients with scalp psoriasis were treated with calcip...
			Nail Psoriasis. A controlled double-blind comparison of calcipotriene ointment with a combination of betamethasone dipropionate ...
			Pustular Psoriasis. Calcipotriene may be an effective treatment option for pustular psoriasis. One study showed improvement of g...
			Psoriasis in Children. A prospective, double-blind, randomized controlled trial examining calcipotriene in children found no imp...
			High-Dose Calcipotriene. Inpatients with severe psoriasis were treated with 200 g of calcipotriene ointment for 1 week, followed...
		Calcipotriene Plus Betamethasone Dipropionate
			Scalp Psoriasis. A scalp formulation of calcipotriene–betamethasone dipropionate developed for once-daily treatment of scalp pso...
			Nail Psoriasis. In an open-label, uncontrolled study, patients with nail psoriasis treated with the two-compound product of calc...
		Calcitriol
			US Food and Drug Administration-Approved Indication—Psoriasis. Calcitriol is approved for the treatment of mild to moderate plaq...
				Intertriginous Psoriasis. A double-blind, randomized controlled trial showed that calcitriol 3 μg/g was as well tolerated as tac...
				Scalp and Nail Psoriasis. There have been no studies on the efficacy of calcitriol in scalp and nail psoriasis. However, there i...
		Combination Use with Other Antipsoriasis Therapies
			Ultraviolet B and Psoralen Plus Ultraviolet A. Multiple studies have demonstrated that a combination of a vitamin D analog and U...
			Topical Corticosteroids. The combination of vitamin D3 analogs with TCS was discussed previously.51
			Compatibility Study. Q49.8 When combining calcipotriene with another topical agent, the stability of each agent can be altered. ...
			Systemic Treatments. Q49.9 Because of potential toxicities with systemic therapies, calcipotriene has been combined with multipl...
		Off-Label Uses
			Disorders of Keratinization. Q49.10 Calcipotriene was applied to the skin of patients with congenital ichthyosis (including X-li...
			Prurigo Nodularis. A randomized, prospective, double-blind, right-left comparative trial found that calcipotriol ointment was su...
			Morphea. In a 3-month open-label study, patients with morphea or linear scleroderma were treated with calcipotriene under occlus...
			Vitiligo. A placebo-controlled, double-blind study assessing whether the addition of topical calcipotriene to psoralen plus UVA ...
			Other Off-Label Uses. Case reports have documented improvement in multiple disorders with topical calcipotriene use. These inclu...
		Adverse Effects
			Hypercalcemia. Q49.11 The greatest concern with the use of topical vitamin D preparations is their potential to cause hypercalce...
			Irritation. The application of calcipotriene can cause lesional and perilesional irritation. Irritation is self-limiting and res...
			Photosensitivity. Q49.12 Mild photosensitivity has been reported in psoriatic patients treated with a combination of calcipotrie...
			Allergic Contact Dermatitis. Q49.12 Evidence suggests that calcipotriene is both a weak contact allergen and a contact irritant....
	Bibliography: Important Reviews and Chapters
	References*
PART X Miscellaneous Topical Drugs
50 -

Sunscreens
	50 - Sunscreens
		Introduction
		Sunscreen Options
			Active Sunscreen Ingredients
			Ultraviolet B Sunscreens
			Ultraviolet A Sunscreens
			Physical Blockers
			Sunscreens Pending Approval
		Clinical Use
			Indications
			Sun Protection Factor Level
			Ultraviolet A Protection
			Sunscreen Vehicles
			Adverse Effects
			Special Patient Group Instructions
			Theoretical Inhibition of Vitamin D Synthesis
			Sunless Tanners—Dihydroxyacetone
		Summary
		Bibliography: Important Reviews and Chapters
		References*
51 - Therapeutic Shampoos
	Introduction
	Dermatoses Involving the Scalp
		Historical Perspective
		Pharmacology
			Mechanism of Action
			Systemic Absorption
		Clinical Use
		Contraindications
		Adverse Effects
		Safety in Pregnancy and Lactation
		Safety in Children
	Therapeutic Guidelines
		General Considerations
		Management Strategy
		Role in Systemic Therapy
		Drug Interactions
		Therapeutic Monitoring
	Summary
	Bibliography: Important Reviews and Chapters
	References*
	Web References
52 - α-Hydroxy Acids
	Introduction
	Pharmacology
		Structure
		Mechanism of Action
		Polyhydroxy Acids Effects
	Clinical Use
		Xerosis and Ichthyosis
		Hyperpigmentation and Pigmented Lesions
		Acne Vulgaris and Related Conditions
		Psoriasis
		Nail Disorders
		Actinic Keratoses
		α-Hydroxy Acid in Chemical Peels
	Formulations and Bioavailability
	Safety and Adverse Effects
		Irritation and Pigmentary Changes
		Photosensitivity
		Herpes Simplex Infections
	Summary
	Bibliography: Important Reviews and Chapters
	References*
53 - Chemical Peels
	Introduction
	Superficial Chemical Peels
		α-Hydroxy Acids
		β-Hydroxy Acids
		Jessner’s Solution
	Medium-Depth Chemical Peels
		Combination Peels
	Deep Chemical Peels
		Clinical Use
	Bibliography: Important Reviews and Chapters
	References*
54 - Products for the Care of Chronic Wounds
	Introduction
	Wound Healing Physiology and Ideal Wound Healing Environment
	General Approach to a Patient with Chronic Wounds
		Wound History
		Past Medical History
		Past Surgical History
		Medication History
		Social History
		Review of Systems
		Physical Examination
		Laboratory Evaluation
	Venous Ulcer Disease
		Compression Therapy for Venous Leg Ulcers
		Wound Bed Preparation
	Systemic and Surgical Treatments
		Pentoxifylline
		Surgical Therapy
		Growth Factor Therapy
	Bibliography: Important Reviews and Chapters
	References*
55 - Agents Used for Treatment of Hyperkeratosis
	Introduction
	Salicylic Acid
		Pharmacology
			Mechanism of Action
		Clinical Use
			Adverse Effects
	Sulfur
		Pharmacology
			Mechanism of Action
		Clinical Use
	Tar
		Pharmacology
		Clinical Use
			Adverse Effects
	Urea
		Pharmacology
			Mechanism of Action
		Clinical Use
			Dermatologic Uses
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
56 - Irritants and Allergens: When to Suspect Topical Therapeutic Agents
	Introduction
	Contact Dermatitis: the Concept
		Allergic Contact Dermatitis
		Irritant Contact Dermatitis
	When to Suspect Contact Dermatitis
		Regional Approach
	Final Thoughts
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
57 - Miscellaneous Topical Agents
	Introduction
	Topical Antioxidants
		Ascorbic Acid (Vitamin C)
			Pharmacology
			Clinical Use
		Vitamin E
			Pharmacology
			Clinical Use
		Selenium
		Zinc
		Aluminum Chloride
			Pharmacology
			Clinical Use
		Ferric Subsulfate
	Other Topical Agents
		Phytonadione (Vitamin K1)
			Pharmacology
			Clinical Use
		Minoxidil
			Pharmacology
			Clinical Use
		Bimatoprost
		Capsaicin
		Anthralin
			Pharmacology
			Clinical Use
				Off-Label Dermatologic Uses
		Aloe Vera
		Brimonidine
			Pharmacology
			Clinical Use
				Off-Label Dermatologic Uses
		Oxymetazoline
			Pharmacology
			Clinical Use
		Hydrogen Peroxide
	Bibliography: Important Reviews and Chapters
	References*
PART XI Injectable and Mucosal Routes of Drug Administration
58 - Local Anesthetics
	Introduction
	Injectable Local Anesthetics
		Lidocaine and Related Amide Anesthetics
		Pharmacology
			Mechanism of Action
		Clinical Use
			Off-Label Dermatologic Uses
			Therapeu\tic Guidelines
	Topical Anesthetics
		Eutectic Lidocaine and Prilocaine
			Pharmacology
			Clinical Use
				Off-label Dermatologic Uses
		Topical Lidocaine
		Benzocaine
		Dyclonine
	Coinjectable Vasoconstrictors
		Epinephrine
			Pharmacology
			Clinical Use
				Adverse Effects
				Drug Interactions
	Other Agents with Local Anesthetic Effects
		Capsaicin
			Clinical Use
		Diphenhydramine
	Bibliography: Important Reviews and Chapters
	References*
59 - Injectable Dermal and Subcutaneous Fillers
	Introduction
	Categories of Dermal Fillers
		Collagen
		Hyaluronic Acid
		Calcium Hydroxyapatite
		Poly-L-Lactic Acid
		Polymethylmethacrylate
		Silicone
	Autologous Human Fibroblasts
	Fillers on the Horizon
	Adverse Effects
		Immediate Adverse Effects (0–2 Days)
		Early Adverse Effects (3–14 Days)
		Late Adverse Effects (15 Days–1 Year)
		Delayed (>1 Year)
	Acknowledgment
	Bibliography: Important Reviews and Chapters
	References*
60 - Botulinum Toxin Injections
	Introduction and History
		Pharmacology
			Mechanism of Action
		Clinical Use
			Indications
			Adverse Effects
			Therapeutic Guidelines
	Conclusions
	Bibliography: Important Reviews and Chapters
	References*
61 - Oral Mucosal Therapeutics
	Introduction
	Review of Common Terminology
	Erosive Gingivostomatitis
		Mouth Rinses
		Topical Therapy
			Corticosteroids
			Steroid-Sparing Immunosuppressants
			Topical Anesthetics
			Intralesional Corticosteroids
		Systemic Therapy
	Herpetic Gingivostomatitis
		Topical Therapy
	Oral Candidiasis
		Tips and Clinical Pearls—Oral Candidiasis
		Topical Therapy
		Systemic Therapy
	Hairy Tongue
		Topical Therapy
	Recurrent Aphthous Stomatitis
		Topical Therapy
		Intralesional Corticosteroids
		Systemic Therapy
		Anti-inflammatory Agents
		Immunobiologic Agents
		Tips and Clinical Pearls—Anug
		Topical Therapy
		Systemic Therapy
	Mucositis (Stomatitis)
		Tips and Clinical Pearls—Mucositis
		Topical Therapy
		Systemic Therapy
	Xerostomia
		Tips and Clinical Pearls—Xerostomia
			Topical Therapy
				Anesthetics and coating agents
				Antimicrobials
				Anti-inflammatory agents
			Systemic Therapy. Q61.10
	Burning Mouth Syndrome
		Topical Therapy
			Systemic Therapy. Q61.11
PART XII Major Adverse Effects From Systemic Drugs
62 - Hepatotoxicity of Dermatologic Drug Therapy
	Introduction
	The Liver and Drug Metabolism
		Hepatic Drug Metabolism
		Polymorphisms
	Mechanisms of Drug Hepatotoxicity
		General Mechanisms Involved
		Toxic Versus Idiosyncratic Reactions
	Risk Factors for Drug Hepatotoxicity
		General Risk Factors
		Drug-Specific Risk Factors
		Predictive Testing for Polymorphisms
	Drug Information Dissemination Issues
		Risk with Real World Drug Use
		Potential Predictors of Hepatotoxicity
	Classification Systems
	Drug Etiologies
		Common Dermatologic Drug Etiologies
		Less Common Drug Etiologies
	Diagnosis
		Diagnostic Algorithm
		Differential Diagnosis
		Referral Criteria
		Liver ‘Function’ Tests
	Management
		Background Issues
		Management Options
	Looking to the Future—Lessons from the Past
	Bibliography: Important Reviews and Chapters
	References*
63 - Hematologic Toxicity of Drug Therapy
	Introduction
	General Principles
		Mechanisms of Hematologic Toxicities
		Timing of Hematologic Toxicity
		Prediction of Risk for Hematologic Toxicities
		Agranulocytosis
		Aplastic Anemia (Pancytopenia)
		Thrombocytopenia
		Neoplasia
		Methotrexate
		Azathioprine
		Cyclophosphamide
		Chlorambucil
		Hydroxyurea
		Interferons
		Dapsone
		Sulfonamides
			Sulfasalazine
			Trimethoprim-Sulfamethoxazole
		Antimalarials
		Colchicine
		Gold and Penicillamine
		Mycophenolate Mofetil
		Rituximab
		Miscellaneous Drugs
	Treatment of Hematologic Toxicities
		Guidelines for Drug Cessation and Rechallenge
		Transfusion Criteria
		Management of Agranulocytosis
	Bibliography: Important Reviews and Chapters
	References*
64 - Drug-Induced Malignancy
	Introduction
	Assessment of Drug Causation for Malignancy Induction
		General Principles and a Drug Causation Determination Algorithm
		Entire Population Versus Disease-Specific Databases
		Comparisons with Drug-Specific Databases
	General Principles of Carcinogenesis
		Multistep Model of Carcinogenesis
		Oncogenes and Tumor Suppressor Genes
	Review of Malignancy Risk with Organ Transplantation
		Malignancies Having Increased Risk with Organ Transplantation
		Viral Cofactors
		Rheumatoid Arthritis
		Inflammatory Bowel Disease
		Multiple Sclerosis
		Psoriasis
	Specific Drugs Used in Dermatology and their Potential Risk for Malignancy
		Alkylating Agents—Cyclophosphamide and Chlorambucil
		Antimetabolites—Azathioprine and Methotrexate
		Calcineurin Inhibitors—Cyclosporine
		Biologic Therapies for Psoriasis—Tumor Necrosis Factor Inhibitors
		Psoralen and Ultraviolet a Photochemotherapy Versus Organ Transplantation Squamous Cell Carcinoma and Melanoma Risk
	Prevention and Detection of Possible Malignancies
		Cyclophosphamide
		Psoralen and Ultraviolet A and Organ Transplantation Patients
		Biologic Therapies and Cyclosporine
	The Bottom Line
	Bibliography: Important Reviews and Chapters
	References*
65 - Dermatologic Drugs During Pregnancy and Lactation
	Introduction
	General Principles
		Sources for Information—Drug Use in Pregnancy and Lactation
		Risk Related to Time of Drug Consumption
		Timing—Before Conception
		Timing—First Trimester
		Timing—Second Trimester
		Timing—Third Trimester and Preterm
		Timing—During Lactation
	Guide for Specific Drug Use
	Summary
	References*
	Web References
66 - Drug Interactions
	Introduction
	General Principles of Drug Interactions
		Potential Consequences of Drug–Drug Interactions
		Absorption
		Distribution
		P-Glycoprotein (Fig. 66.2)
		Metabolism
		Excretion
	Cytochrome P-450–Based Drug Interactions
		Cytochrome P-450 Enzymes Background Information
		Induction of Cytochrome P-450 3A4
		Inhibition of CYP3A4
	Drug Interaction Risks by Drug Category
		Azole Antifungals
		Allylamine Antifungals
		Azathioprine
		Colchicine
		Cyclosporine
		Grapefruit Juice
		Herbal Remedies
		HMG CoA Reductase Inhibitors
		Macrolide Antibiotics
		Methotrexate
		Hormonal Contraceptives
		Pimozide
		Warfarin
	Genetic Polymorphisms
		Antagonistic Effect
		Synergistic Effects
	Do All Drugs in a Given Class Behave in a Similar Manner?
	Summary
	Bibliography: Important Reviews and Chapters
	References*
67 - Cutaneous Drug Reactions With Systemic Features
	Introduction
		Pseudolymphoma
		Anticonvulsants
			Q67.2 DRESS has been commonly associated with the aromatic anticonvulsants, namely phenytoin, phenobarbital, oxcarbazepine, and ...
		Sulfonamide Antibiotics
		Dapsone
		Minocycline
		Other Drugs
		Differential Diagnosis
		Treatment
		Treatment
	Drug-Induced Lupus
		Minocycline
		Antitumor Necrosis Factor Agents
	General Discussion
PART XIII Special Pharmacology and Therapeutics Topics
68 -

Informed Consent and Risk
Management
	68 - Informed Consent and Risk Management
		Introduction
		Historical Perspective
		Ethical Perspective
		Basic Legal Principles
		Components of Informed Consent
		Systemic Drugs and Informed Consent
		Optimizing Patient Understanding
		Medicolegal Risk Management
		Dermatology Malpractice
		Summary
		References*
		Web References
69 - Compounding in Dermatology
	Introduction
	The Compounding Triad
		The Patient
		The Pharmacist
		The Physician
	Developing a Stable Compounding Formula
		Clinical Evidence
		Feasibility
	Properly Write the Prescription
		Compounding Formula Instructions
		Patient Instructions for use of the Compound
	Monitor the Patient
		Evaluation of the Treatment
		Documentation
		New Mixing Technology Used to Prepare Topical Compounded Preparations12
		Common Topical Compounded Preparations
	Summary
	References*
70 - Dermatologic Drug Therapy in Children
	Introduction
		Pediatric Pearls
		Topical Corticosteroids
		Systemic Corticosteroids
		Beta Blockers
	Systemic Retinoids
		Isotretinoin
		Acitretin
	Systemic Immunosuppressive Therapies
		Methotrexate
		Azathioprine
		Cyclosporine
		Biologic Therapies
		Tumor Necrosis Factor Inhibitors in Children
		Etanercept
		Adalimumab
		Infliximab
	Acknowledgement
	Bibliography: Important Reviews and Chapters
	References*
Appendix
I - Core Questions for Understanding Systemic Dermatologic Drugs
	Section 1—Pharmacology Basic Science
	Section 2—Clinical Use
	Section 3—Severe Adverse Effects
	Section 4. Less Serious Adverse Effects
	Section 5 - Drug Safety Monitoring
	Section 6—Drug Interactions (see also Appendix 2)
	Section 7—Miscellaneous Issues
Appendix
II - The Most Potentially Serious Drug Interactions
	General Principles for Creating This Appendix
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Z