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From time to time, Joslyn Kirby, MD, asks other physicians about their experience with certain medications used in dermatology, especially when something new hits the market.
“Sometimes I get an answer like, ‘The last time I used that medicine, my patient needed a liver transplant,’ ” Dr. Kirby, associate professor of dermatology, Penn State University, Hershey, said during the Orlando Dermatology Aesthetic and Clinical Conference. “It’s typically a story of something rare, uncommon, and awful. The challenge with an anecdote is that for all its power, it has a lower level of evidence. But it sticks with us and influences us more than a better level of evidence because it’s a situation and a story that we might relate to.”
Dr. Kirby said that when she thinks about managing side effects from drugs used in dermatology, it usually relates to something common and low-risk such as sore, dry skin with isotretinoin use. In contrast, if there is an uncommon but serious side effect, then mitigation rather than management is key. “I want to mitigate the risk – meaning warn my patient about it or be careful about how I select my patients when it is a serious side effect that happens infrequently,” she said. “The worst combination is a frequent and severe side effect. That is something we should avoid, for sure.”
Isotretinoin
But another aspect of prescribing a new drug for patients can be less clear-cut, Dr. Kirby continued, such as the rationale for routine lab monitoring. She began by discussing one of her male patients with moderate to severe acne. After he failed oral antibiotics and topical retinoids, she recommended isotretinoin, which carries a risk of hypertriglyceridemia-associated pancreatitis. “Early in my career, I was getting a lot of monthly labs in patients on this drug that were totally normal and not influencing my practice,” Dr. Kirby recalled. “We’ve seen studies coming out on isotretinoin lab monitoring, showing us that we can keep our patients safe and that we really don’t need to be checking labs as often, because lab changes are infrequent.”
In one of those studies, researchers evaluated 1,863 patients treated with isotretinoin for acne between Jan. 1, 2008, and June 30, 2017 (J Am Acad Dermatol. 2020 Jan;82[1]:72-9).Over time, fewer than 1% of patients screened developed grade 3 or greater triglyceride testing abnormalities, while fewer than 0.5% developed liver function testing (LFT) abnormalities. Authors of a separate systematic review concluded that for patients on isotretinoin therapy without elevated baseline triglycerides, or risk thereof, monitoring triglycerides is of little value (Br J Dermatol. 2017 Oct;177[4]:960-6). Of the 25 patients in the analysis who developed pancreatitis on isotretinoin, only 3 had elevated triglycerides at baseline.
“I was taught that I need to check triglycerides frequently due to the risk of pancreatitis developing with isotretinoin use,” Dr. Kirby said. “Lipid changes on therapy are expected, but they tend to peak early, meaning the first 3 months of treatment when we’re ramping up from a starting dose to a maintenance dose. It’s rare for somebody to be a late bloomer, meaning that they have totally normal labs in the first 3 months and then suddenly develop an abnormality. People are either going to demonstrate an abnormality early or not have one at all.”
When Dr. Kirby starts patients on isotretinoin, she orders baseline LFTs and a lipid panel and repeats them 60 days later. “If everything is fine or only mildly high, we don’t do more testing, only a review of systems,” she said. “This is valuable to our patients because fear of needles and fainting peak during adolescence.”
Spironolactone
The clinical use of regularly monitoring potassium levels in young women taking spironolactone for acne has also been questioned. The drug has been linked to an increased risk for hyperkalemia, but the prevalence is unclear. “I got a lot of normal potassium levels in these patients [when] I was in training and I really questioned, ‘Why am I doing this? What is the rationale?’ ” Dr. Kirby said.
In a study that informed her own practice, researchers reviewed the rate of hyperkalemia in 974 healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne between Dec. 1, 2000, and March 31, 2014 (JAMA Dermatol. 2015 Sep;151[9]:941-4). Of the total of 1,802 serum potassium measurements taken during treatment, 13 (0.72%) were mildly elevated levels and none of the patients had a potassium level above 5.5 mEq/L. Retesting within 1 to 3 weeks in 6 of 13 patients with elevated levels found that potassium levels were normal. “The recommendation for spironolactone in healthy women is not to check the potassium level,” Dr. Kirby said, adding that she does counsel patients about the risk of breast tenderness (which can occur 5% to 40% of the time) and spotting (which can occur in 10% to 20% of patients). Gynecomastia can occur in 10% to 30% of men, which is one of the reasons she does not use spironolactone in male patients.
TB testing and biologics
Whether or not to test for TB in patients with psoriasis taking biologic therapies represents another conundrum, she continued. Patients taking biologics are at risk of reactivation of latent TB infection, but in her experience, package inserts contain language like “perform TB testing at baseline, then periodically,” or “use at baseline, then with active TB symptoms,” and “after treatment is discontinued.”
“What the inserts didn’t recommend was to perform TB testing every year, which is what my routine had been,” Dr. Kirby said. “In the United States, thankfully we don’t have a lot of TB.” In a study that informed her own practice, researchers at a single academic medical center retrospectively reviewed the TB seroconversion rate among 316 patients treated with second-generation biologics (J Am Acad Dermatol. 2020 Oct 1;S0190-9622[20]32676-1. doi: 10.1016/j.jaad.2020.09.075). It found that only six patients (2%) converted and had a positive TB test later during treatment with the biologic. “Of these six people, all had grown up outside the U.S., had traveled outside of the U.S., or were in a group living situation,” said Dr. Kirby, who was not affiliated with the study.
“This informs our rationale for how we can do this testing. If insurance requires it every year, fine. But if they don’t, I ask patients about travel, about their living situation, and how they’re feeling. If everything’s going great, I don’t order TB testing. I do favor the interferon-gamma release assays because they’re a lot more effective than PPDs [purified protein derivative skin tests]. Also, PPDs are difficult for patients who have a low rate of returning to have that test read.”
Terbinafine for onychomycosis
Dr. Kirby also discussed the rationale for ordering regular LFTs in patients taking terbinafine for onychomycosis. “There is a risk of drug-induced liver injury from taking terbinafine, but it’s rare,” she said. “Can we be thoughtful about which patients we expose?”
Evidence suggests that patients with hyperkeratosis greater than 2 mm, with nail matrix involvement, with 50% or more of the nail involved, or having concomitant peripheral vascular disease and diabetes are recalcitrant to treatment with terbinafine
(J Am Acad Dermatol. 2019 Apr;80[4]:853-67). “If we can frame this risk, then we can frame it for our patients,” she said. “We’re more likely to cause liver injury with an antibiotic. When it comes to an oral antifungal, itraconazole is more likely than terbinafine to cause liver injury. The rate of liver injury with terbinafine is only about 2 out of 100,000. It’s five times more likely with itraconazole and 21 times more likely with Augmentin.”
She recommends obtaining a baseline LFT in patients starting terbinafine therapy “to make sure their liver is normal from the start.” In addition, she advised, “let them know that there is a TB seroconversion risk of about 1 in 50,000 people, and that if it happens there would be symptomatic changes. They would maybe notice pruritus and have a darkening in their urine, and they’d have some flu-like symptoms, which would mean stop the drug and get some care.”
Dr. Kirby emphasized that a patient’s propensity for developing drug-induced liver injury from terbinafine use is not predictable from LFT monitoring. “What you’re more likely to find is an asymptomatic LFT rise in about 1% of people,” she said.
She disclosed that she has received honoraria from AbbVie, ChemoCentryx, Incyte, Janssen, Novartis, and UCB Pharma.
From time to time, Joslyn Kirby, MD, asks other physicians about their experience with certain medications used in dermatology, especially when something new hits the market.
“Sometimes I get an answer like, ‘The last time I used that medicine, my patient needed a liver transplant,’ ” Dr. Kirby, associate professor of dermatology, Penn State University, Hershey, said during the Orlando Dermatology Aesthetic and Clinical Conference. “It’s typically a story of something rare, uncommon, and awful. The challenge with an anecdote is that for all its power, it has a lower level of evidence. But it sticks with us and influences us more than a better level of evidence because it’s a situation and a story that we might relate to.”
Dr. Kirby said that when she thinks about managing side effects from drugs used in dermatology, it usually relates to something common and low-risk such as sore, dry skin with isotretinoin use. In contrast, if there is an uncommon but serious side effect, then mitigation rather than management is key. “I want to mitigate the risk – meaning warn my patient about it or be careful about how I select my patients when it is a serious side effect that happens infrequently,” she said. “The worst combination is a frequent and severe side effect. That is something we should avoid, for sure.”
Isotretinoin
But another aspect of prescribing a new drug for patients can be less clear-cut, Dr. Kirby continued, such as the rationale for routine lab monitoring. She began by discussing one of her male patients with moderate to severe acne. After he failed oral antibiotics and topical retinoids, she recommended isotretinoin, which carries a risk of hypertriglyceridemia-associated pancreatitis. “Early in my career, I was getting a lot of monthly labs in patients on this drug that were totally normal and not influencing my practice,” Dr. Kirby recalled. “We’ve seen studies coming out on isotretinoin lab monitoring, showing us that we can keep our patients safe and that we really don’t need to be checking labs as often, because lab changes are infrequent.”
In one of those studies, researchers evaluated 1,863 patients treated with isotretinoin for acne between Jan. 1, 2008, and June 30, 2017 (J Am Acad Dermatol. 2020 Jan;82[1]:72-9).Over time, fewer than 1% of patients screened developed grade 3 or greater triglyceride testing abnormalities, while fewer than 0.5% developed liver function testing (LFT) abnormalities. Authors of a separate systematic review concluded that for patients on isotretinoin therapy without elevated baseline triglycerides, or risk thereof, monitoring triglycerides is of little value (Br J Dermatol. 2017 Oct;177[4]:960-6). Of the 25 patients in the analysis who developed pancreatitis on isotretinoin, only 3 had elevated triglycerides at baseline.
“I was taught that I need to check triglycerides frequently due to the risk of pancreatitis developing with isotretinoin use,” Dr. Kirby said. “Lipid changes on therapy are expected, but they tend to peak early, meaning the first 3 months of treatment when we’re ramping up from a starting dose to a maintenance dose. It’s rare for somebody to be a late bloomer, meaning that they have totally normal labs in the first 3 months and then suddenly develop an abnormality. People are either going to demonstrate an abnormality early or not have one at all.”
When Dr. Kirby starts patients on isotretinoin, she orders baseline LFTs and a lipid panel and repeats them 60 days later. “If everything is fine or only mildly high, we don’t do more testing, only a review of systems,” she said. “This is valuable to our patients because fear of needles and fainting peak during adolescence.”
Spironolactone
The clinical use of regularly monitoring potassium levels in young women taking spironolactone for acne has also been questioned. The drug has been linked to an increased risk for hyperkalemia, but the prevalence is unclear. “I got a lot of normal potassium levels in these patients [when] I was in training and I really questioned, ‘Why am I doing this? What is the rationale?’ ” Dr. Kirby said.
In a study that informed her own practice, researchers reviewed the rate of hyperkalemia in 974 healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne between Dec. 1, 2000, and March 31, 2014 (JAMA Dermatol. 2015 Sep;151[9]:941-4). Of the total of 1,802 serum potassium measurements taken during treatment, 13 (0.72%) were mildly elevated levels and none of the patients had a potassium level above 5.5 mEq/L. Retesting within 1 to 3 weeks in 6 of 13 patients with elevated levels found that potassium levels were normal. “The recommendation for spironolactone in healthy women is not to check the potassium level,” Dr. Kirby said, adding that she does counsel patients about the risk of breast tenderness (which can occur 5% to 40% of the time) and spotting (which can occur in 10% to 20% of patients). Gynecomastia can occur in 10% to 30% of men, which is one of the reasons she does not use spironolactone in male patients.
TB testing and biologics
Whether or not to test for TB in patients with psoriasis taking biologic therapies represents another conundrum, she continued. Patients taking biologics are at risk of reactivation of latent TB infection, but in her experience, package inserts contain language like “perform TB testing at baseline, then periodically,” or “use at baseline, then with active TB symptoms,” and “after treatment is discontinued.”
“What the inserts didn’t recommend was to perform TB testing every year, which is what my routine had been,” Dr. Kirby said. “In the United States, thankfully we don’t have a lot of TB.” In a study that informed her own practice, researchers at a single academic medical center retrospectively reviewed the TB seroconversion rate among 316 patients treated with second-generation biologics (J Am Acad Dermatol. 2020 Oct 1;S0190-9622[20]32676-1. doi: 10.1016/j.jaad.2020.09.075). It found that only six patients (2%) converted and had a positive TB test later during treatment with the biologic. “Of these six people, all had grown up outside the U.S., had traveled outside of the U.S., or were in a group living situation,” said Dr. Kirby, who was not affiliated with the study.
“This informs our rationale for how we can do this testing. If insurance requires it every year, fine. But if they don’t, I ask patients about travel, about their living situation, and how they’re feeling. If everything’s going great, I don’t order TB testing. I do favor the interferon-gamma release assays because they’re a lot more effective than PPDs [purified protein derivative skin tests]. Also, PPDs are difficult for patients who have a low rate of returning to have that test read.”
Terbinafine for onychomycosis
Dr. Kirby also discussed the rationale for ordering regular LFTs in patients taking terbinafine for onychomycosis. “There is a risk of drug-induced liver injury from taking terbinafine, but it’s rare,” she said. “Can we be thoughtful about which patients we expose?”
Evidence suggests that patients with hyperkeratosis greater than 2 mm, with nail matrix involvement, with 50% or more of the nail involved, or having concomitant peripheral vascular disease and diabetes are recalcitrant to treatment with terbinafine
(J Am Acad Dermatol. 2019 Apr;80[4]:853-67). “If we can frame this risk, then we can frame it for our patients,” she said. “We’re more likely to cause liver injury with an antibiotic. When it comes to an oral antifungal, itraconazole is more likely than terbinafine to cause liver injury. The rate of liver injury with terbinafine is only about 2 out of 100,000. It’s five times more likely with itraconazole and 21 times more likely with Augmentin.”
She recommends obtaining a baseline LFT in patients starting terbinafine therapy “to make sure their liver is normal from the start.” In addition, she advised, “let them know that there is a TB seroconversion risk of about 1 in 50,000 people, and that if it happens there would be symptomatic changes. They would maybe notice pruritus and have a darkening in their urine, and they’d have some flu-like symptoms, which would mean stop the drug and get some care.”
Dr. Kirby emphasized that a patient’s propensity for developing drug-induced liver injury from terbinafine use is not predictable from LFT monitoring. “What you’re more likely to find is an asymptomatic LFT rise in about 1% of people,” she said.
She disclosed that she has received honoraria from AbbVie, ChemoCentryx, Incyte, Janssen, Novartis, and UCB Pharma.
From time to time, Joslyn Kirby, MD, asks other physicians about their experience with certain medications used in dermatology, especially when something new hits the market.
“Sometimes I get an answer like, ‘The last time I used that medicine, my patient needed a liver transplant,’ ” Dr. Kirby, associate professor of dermatology, Penn State University, Hershey, said during the Orlando Dermatology Aesthetic and Clinical Conference. “It’s typically a story of something rare, uncommon, and awful. The challenge with an anecdote is that for all its power, it has a lower level of evidence. But it sticks with us and influences us more than a better level of evidence because it’s a situation and a story that we might relate to.”
Dr. Kirby said that when she thinks about managing side effects from drugs used in dermatology, it usually relates to something common and low-risk such as sore, dry skin with isotretinoin use. In contrast, if there is an uncommon but serious side effect, then mitigation rather than management is key. “I want to mitigate the risk – meaning warn my patient about it or be careful about how I select my patients when it is a serious side effect that happens infrequently,” she said. “The worst combination is a frequent and severe side effect. That is something we should avoid, for sure.”
Isotretinoin
But another aspect of prescribing a new drug for patients can be less clear-cut, Dr. Kirby continued, such as the rationale for routine lab monitoring. She began by discussing one of her male patients with moderate to severe acne. After he failed oral antibiotics and topical retinoids, she recommended isotretinoin, which carries a risk of hypertriglyceridemia-associated pancreatitis. “Early in my career, I was getting a lot of monthly labs in patients on this drug that were totally normal and not influencing my practice,” Dr. Kirby recalled. “We’ve seen studies coming out on isotretinoin lab monitoring, showing us that we can keep our patients safe and that we really don’t need to be checking labs as often, because lab changes are infrequent.”
In one of those studies, researchers evaluated 1,863 patients treated with isotretinoin for acne between Jan. 1, 2008, and June 30, 2017 (J Am Acad Dermatol. 2020 Jan;82[1]:72-9).Over time, fewer than 1% of patients screened developed grade 3 or greater triglyceride testing abnormalities, while fewer than 0.5% developed liver function testing (LFT) abnormalities. Authors of a separate systematic review concluded that for patients on isotretinoin therapy without elevated baseline triglycerides, or risk thereof, monitoring triglycerides is of little value (Br J Dermatol. 2017 Oct;177[4]:960-6). Of the 25 patients in the analysis who developed pancreatitis on isotretinoin, only 3 had elevated triglycerides at baseline.
“I was taught that I need to check triglycerides frequently due to the risk of pancreatitis developing with isotretinoin use,” Dr. Kirby said. “Lipid changes on therapy are expected, but they tend to peak early, meaning the first 3 months of treatment when we’re ramping up from a starting dose to a maintenance dose. It’s rare for somebody to be a late bloomer, meaning that they have totally normal labs in the first 3 months and then suddenly develop an abnormality. People are either going to demonstrate an abnormality early or not have one at all.”
When Dr. Kirby starts patients on isotretinoin, she orders baseline LFTs and a lipid panel and repeats them 60 days later. “If everything is fine or only mildly high, we don’t do more testing, only a review of systems,” she said. “This is valuable to our patients because fear of needles and fainting peak during adolescence.”
Spironolactone
The clinical use of regularly monitoring potassium levels in young women taking spironolactone for acne has also been questioned. The drug has been linked to an increased risk for hyperkalemia, but the prevalence is unclear. “I got a lot of normal potassium levels in these patients [when] I was in training and I really questioned, ‘Why am I doing this? What is the rationale?’ ” Dr. Kirby said.
In a study that informed her own practice, researchers reviewed the rate of hyperkalemia in 974 healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne between Dec. 1, 2000, and March 31, 2014 (JAMA Dermatol. 2015 Sep;151[9]:941-4). Of the total of 1,802 serum potassium measurements taken during treatment, 13 (0.72%) were mildly elevated levels and none of the patients had a potassium level above 5.5 mEq/L. Retesting within 1 to 3 weeks in 6 of 13 patients with elevated levels found that potassium levels were normal. “The recommendation for spironolactone in healthy women is not to check the potassium level,” Dr. Kirby said, adding that she does counsel patients about the risk of breast tenderness (which can occur 5% to 40% of the time) and spotting (which can occur in 10% to 20% of patients). Gynecomastia can occur in 10% to 30% of men, which is one of the reasons she does not use spironolactone in male patients.
TB testing and biologics
Whether or not to test for TB in patients with psoriasis taking biologic therapies represents another conundrum, she continued. Patients taking biologics are at risk of reactivation of latent TB infection, but in her experience, package inserts contain language like “perform TB testing at baseline, then periodically,” or “use at baseline, then with active TB symptoms,” and “after treatment is discontinued.”
“What the inserts didn’t recommend was to perform TB testing every year, which is what my routine had been,” Dr. Kirby said. “In the United States, thankfully we don’t have a lot of TB.” In a study that informed her own practice, researchers at a single academic medical center retrospectively reviewed the TB seroconversion rate among 316 patients treated with second-generation biologics (J Am Acad Dermatol. 2020 Oct 1;S0190-9622[20]32676-1. doi: 10.1016/j.jaad.2020.09.075). It found that only six patients (2%) converted and had a positive TB test later during treatment with the biologic. “Of these six people, all had grown up outside the U.S., had traveled outside of the U.S., or were in a group living situation,” said Dr. Kirby, who was not affiliated with the study.
“This informs our rationale for how we can do this testing. If insurance requires it every year, fine. But if they don’t, I ask patients about travel, about their living situation, and how they’re feeling. If everything’s going great, I don’t order TB testing. I do favor the interferon-gamma release assays because they’re a lot more effective than PPDs [purified protein derivative skin tests]. Also, PPDs are difficult for patients who have a low rate of returning to have that test read.”
Terbinafine for onychomycosis
Dr. Kirby also discussed the rationale for ordering regular LFTs in patients taking terbinafine for onychomycosis. “There is a risk of drug-induced liver injury from taking terbinafine, but it’s rare,” she said. “Can we be thoughtful about which patients we expose?”
Evidence suggests that patients with hyperkeratosis greater than 2 mm, with nail matrix involvement, with 50% or more of the nail involved, or having concomitant peripheral vascular disease and diabetes are recalcitrant to treatment with terbinafine
(J Am Acad Dermatol. 2019 Apr;80[4]:853-67). “If we can frame this risk, then we can frame it for our patients,” she said. “We’re more likely to cause liver injury with an antibiotic. When it comes to an oral antifungal, itraconazole is more likely than terbinafine to cause liver injury. The rate of liver injury with terbinafine is only about 2 out of 100,000. It’s five times more likely with itraconazole and 21 times more likely with Augmentin.”
She recommends obtaining a baseline LFT in patients starting terbinafine therapy “to make sure their liver is normal from the start.” In addition, she advised, “let them know that there is a TB seroconversion risk of about 1 in 50,000 people, and that if it happens there would be symptomatic changes. They would maybe notice pruritus and have a darkening in their urine, and they’d have some flu-like symptoms, which would mean stop the drug and get some care.”
Dr. Kirby emphasized that a patient’s propensity for developing drug-induced liver injury from terbinafine use is not predictable from LFT monitoring. “What you’re more likely to find is an asymptomatic LFT rise in about 1% of people,” she said.
She disclosed that she has received honoraria from AbbVie, ChemoCentryx, Incyte, Janssen, Novartis, and UCB Pharma.
FROM ODAC 2021