The FDA has approved a 0.3% foam formulation of the phosphodiesterase-4 (PDE4) inhibitor roflumilast (Zoryve – Arcutis) for topical treatment of seborrheic dermatitis in patients ≥9 years old. Roflumilast is the first PDE4 inhibitor to be approved in the US for this indication. It is also available in a 0.3% cream formulation (Zoryve) for treatment of plaque psoriasis and in an oral formulation (Daliresp, and generics) for treatment of chronic obstructive pulmonary disease. A 0.15% cream formulation for treatment of atopic dermatitis in patients ≥6 years old will be reviewed by the FDA in July.

The FDA has approved Verkazia (Santen), a 0.1% ophthalmic emulsion formulation of the calcineurin inhibitor cyclosporine, for treatment of vernal keratoconjunctivitis (VKC). Verkazia is the first product to be approved in the US for this indication.

The 1.5% cream formulation of the Janus kinase (JAK) inhibitor ruxolitinib (Opzelura – Incyte) has been approved by the FDA for topical treatment of nonsegmental vitiligo (NSV) in patients ≥12 years old. Opzelura is the first product to be approved by the FDA for this indication. It was previously approved for treatment of atopic dermatitis.

Efgartigimod alfa-fcab (Vyvgart – Argenx), a first-in-class neonatal Fc receptor (FcRn) antagonist, has been approved by the FDA for IV treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. The IV complement inhibitor eculizumab (Soliris) was approved for the same indication in 2017.

The FDA has approved a 1.5% topical cream formulation of the Janus kinase (JAK) inhibitor ruxolitinib (Opzelura – Incyte) for short-term, non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients ≥12 years old whose disease has not been adequately controlled with other topical prescription drugs. Ruxolitinib is the first JAK inhibitor to be approved for topical use and the first to be approved in the US for treatment of AD. An oral formulation of ruxolitinib (Jakafi) is approved for treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease.

The B-lymphocyte stimulator (BLyS)-specific inhibitor belimumab (Benlysta – GSK), which was approved earlier for treatment of active, autoantibody-positive, nonrenal, systemic lupus erythematosus (SLE), has now been approved for use in addition to standard therapy for treatment of active lupus nephritis in adults. Belimumab is the first drug to be approved in the US for treatment of both SLE and lupus nephritis.

Voclosporin (Lupkynis – Aurinia), an oral calcineurin inhibitor, has been approved by the FDA for use in combination with the antimetabolite immunosuppressant mycophenolate mofetil (Cellcept, and generics) and a corticosteroid for treatment of adults with active lupus nephritis. It is the first calcineurin inhibitor to be approved in the US for this indication. Tacrolimus (Prograf, and others) and cyclosporine (Neoral, and others), the other available systemic calcineurin inhibitors, are approved for prophylaxis of organ rejection in transplant patients.

Atopic dermatitis (AD; also known as eczema) is frequently associated with other atopic disorders such as allergic rhinitis, asthma, and food allergy. It commonly presents in infancy and early childhood and has a relapsing course, often improving by adolescence, but sometimes persisting into (or first appearing in) adulthood or even old age.

Mild to moderate psoriasis can be treated with topical drugs or with phototherapy. Patients with moderate to severe disease generally require systemic therapy.

View Table: Drugs for Ulcerative Colitis

Allergic rhinitis can be classified as seasonal, perennial, or episodic. It is often associated with allergic conjunctivitis, rhinosinusitis, and asthma.

H₁-ANTIHISTAMINES — Oral – Oral second-generation H₁-antihistamines are the preferred first-line treatment for relief of the itching, sneezing, and rhinorrhea that characterize mild-to-moderate allergic rhinitis. They are less effective for nasal congestion.

The FDA has approved dupilumab (Dupixent – Sanofi/Regeneron), a subcutaneously-injected fully human monoclonal antibody, for treatment of adults with moderate to severe atopic dermatitis (eczema) that has not responded to topical therapies. It can be used with or without topical corticosteroids.

The FDA has approved crisaborole 2% ointment (Eucrisa – Pfizer) for topical treatment of mild to moderate atopic dermatitis in patients ≥2 years old. It is the first phosphodiesterase type-4 (PDE4) inhibitor to be approved in the US for this indication.

The FDA has approved Viekira Pak (Abbvie), a fixed-dose combination of two new direct-acting antiviral agents (ombitasvir, paritaprevir) with the pharmacologic enhancer ritonavir in one tablet, co-packaged with a third new direct-acting antiviral agent (dasabuvir) in a second tablet, for oral treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Genotype 1 is responsible for 70-80% of HCV infections in the US.

Aminosalicylates are effective for induction and maintenance of remission in mild to moderate ulcerative colitis. They are not recommended for treatment of Crohn's disease.

FORMULATIONS — Oral mesalamine is rapidly absorbed in the small intestine and most of the drug does not reach the colon. Pentasa releases mesalamine gradually throughout the gastrointestinal tract. Delzicol, Asacol HD, Lialda, and Apriso delay the release of the drug until it reaches the distal ileum and colon. Sulfasalazine (Azulfidine, and generics), balsalazide (Colazal, and others), and olsalazine (Dipentum) are prodrugs; mesalamine is azo-bonded to a second moiety and released in the colon following bacterial cleavage of the bond. Mesalamine is also available as an enema (Rowasa, and generics) and as a rectal suppository (Canasa).

The use of drugs to prevent and control symptoms of allergic disorders can be optimized when patients avoid exposure to specific allergens and/or environmental conditions that trigger or worsen their symptoms.

Drugs for glaucoma, age-related macular degeneration, bacterial conjunctivitis, and dry eyes are reviewed here. Drugs for the treatment of allergic conjunctivitis will be reviewed in a future issue of Treatment Guidelines on Drugs for Allergic Disorders.

Inflammatory bowel disease (IBD) is generally classified as either Crohn’s disease (CD) or ulcerative colitis (UC). More detailed guidelines on their treatment are available from the American College of Gastroenterology.

The FDA has approved belatacept (bel at´ a sept; Nulojix – Bristol-Myers Squibb) for prevention of organ rejection in adult patients receiving a kidney transplant.

Drugs for glaucoma, age-related macular degeneration, bacterial conjunctivitis, and dry eyes are reviewed here. Ophthalmic drugs can have local and systemic adverse effects. In addition, for some elderly patients, the complexity of self-administering numerous ophthalmic drugs may be the limiting factor in their ability to care for themselves. Drugs for the treatment of allergic conjunctivitis will be reviewed in a future issue of Treatment Guidelines on Drugs for Allergic Disorders.

Inflammatory bowel disease (IBD) is either Crohn's disease or ulcerative colitis. Drug selection is guided by disease type (Crohn's versus ulcerative colitis), severity and location and whether the goal is induction or maintenance of remission. Table 1 on page 66 lists the drugs used to treat IBD with their formulations and cost. Table 2 on page 68 lists the drugs of choice and their doses for different indications. Table 3 on page 71 lists the drugs' adverse effects and recommendations for monitoring. More detailed guidelines are available from the American College of Gastroenterology.

The drugs of choice for treatment of some fungal infections are listed in the tables. Some of the indications and dosages recommended here have not been approved by the FDA. Other guidelines are available from the Infectious Diseases Society of America (www.idsociety.org).

Allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria, anaphylaxis and asthma (reviewed in Treatment Guidelines 2005; 3:33 and not included here), are prevalent worldwide, especially in industrialized countries. Pharmacologic treatment of these disorders continues to improve in efficacy and safety. In addition to using drugs to prevent and control the symptoms of their allergic diseases, patients should also be instructed to avoid, if possible, specific allergens and/or environmental conditions that trigger or worsen their symptoms.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

Micafungin sodium (Mycamine - Astellas), the second echinocandin antifungal to become available in the US, has been approved by the FDA for intravenous treatment of esophageal candidiasis and prophylaxis of invasive Candida infections in patients undergoing hematopoietic stem cell transplantation (HSCT).

The FDA issued a public health advisory on March 10, 2005 warning about a risk of cancer with topical formulations of tacrolimus (Protopic) and pimecrolimus (Elidel) used to treat eczema in adults and children more than 2 years old. Elidel has been heavily promoted to the general public on television. The warning was based on reports of dose-related cancer in animals and 29 reports of cancer (including 8 skin malignancies and 12 lymphomas) in adults and children treated with these immunosuppressive drugs. Cause and effect have not been established. When Protopic was first marketed, The Medical Letter warned that the possibility of an increased risk of skin malignancies and lymphoma should be kept in mind (Med Lett Drugs Ther 2001; 43:33).

The drugs of choice for treatment of some fungal infections are listed in the table that begins on page 8. Some of the indications and dosages recommended here have not been approved by the FDA.

Tinidazole (Tindamax - Presutti Labs), an oral antiprotozoal drug similar to metronidazole (Flagyl, and others), has been approved by the FDA for treatment of trichomoniasis in adults and for treatment of giardiasis, intestinal amebiasis and amebic liver abcess in adults and children more than 3 years old. Tinidazole has been widely used outside of the US for decades under the trade name Fasigyn (Pfizer).

Telithromycin (Ketek - Aventis) has been approved by the FDA for oral treatment of mild to moderate community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute bacterial sinusitis in patients age 18 and older. The drug is the first in a new class of antibiotics, the ketolides, derived from the macrolide erythromycin. Telithromycin has been marketed in Europe since 2001.

The ability of grapefruit juice to increase serum concentrations of drugs was first discovered during a study of the effect of ethanol on felodipine (Plendil) pharmacokinetics. Double-strength grapefruit juice used to disguise the taste of ethanol resulted in higher than expected serum concentrations of felodipine (DG Bailey et al, Clin Invest Med 1989; 12:357).

Allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria and anaphylaxis, along with asthma (reviewed in Treatment Guidelines 2002; 1:7 and not included here), have increased in prevalence during the past 30 years and are now epidemic worldwide, especially in industrialized countries. Many safe and effective drugs are currently available for prevention and relief of symptoms in these disorders, but pharmacological treatment alone may not be sufficient. Patients should also be instructed to avoid specific allergens or environmental conditions that trigger their symptoms. Allergen-specific immunotherapy, parenteral administration of gradually increasing doses of the allergen ("allergy shots"), has been effective in allergic rhinitis, allergic conjunctivitis and allergic asthma, and also in prevention of anaphylaxis triggered by stings from bees, yellow jackets, hornets and wasps. It has not been effective in food allergy, atopic dermatitis or urticaria.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

Pimecrolimus 1% cream (pim e kroe' limus; SDZ ASM 981; Elidel - Novartis) has been approved by the FDA for short-term and intermittent long-term treatment of mild to moderate atopic dermatitis in non-immunocompromised patients at least 2 years old.

Sirolimus, whlch is structurally related to tacrolimus, has been approved by the FDA for prevention of acute renal transplant rejection. The manufacturer recommends that sirolimus be taken with cyclosporine and corticosteroids.

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.

The drugs of choice for treatment of deep fungal infections are listed in the table below. Some of the indications and dosages recommended here have not been approved by the FDA.

The drugs of choice for treatment of deep fungal infections are listed in the table on page 101. Some of the indications and dosages recommended here have not been approved by the US Food and Drug Administration. More detailed guidelines are available from the Infectious Diseases Society of America (J Sobel et al, Clin Infect Dis, volume 30, April 2000).

Itraconazole (Sporanox - Janssen), an oral antifungal triazole that has been available in the USA since 1992 for treatment of deep fungal infections (Medical Letter, 35:7, 1993), is now being marketed for treatment of dermatophyte infections of the toenails, with or without fingernail involvement.

Tacrolimus (Prograf - Fujisawa), previously called FK506 (Medical Letter, 33:94, 1991), has been approved by the US Food and Drug Administration for primary prevention of organ rejection in patients receiving liver transplants. The drug has also been used as rescue therapy for organ graft rejection unresponsive to cyclosporine (Sandimmune) and other immunosuppressive drugs.