Stefanie C. Nigro, PharmD, BCACP, CDE, BC-ADM

Information about treatment options discussed for off-label use may have evolved since this case was written on March 26, 2020. Pharmacists should refer to the CDC website for up-to-date information. 

DT, a 45-year-old Caucasian man, comes to the pharmacy with 2 new prescriptions: azithromycin (500 mg daily for 1 day and 250 mg daily for 4 days) and hydroxychloroquine (200 mg 3 times a day for 10 days). He is a longtime patron, so you know his medical history well. DH is being treated for atrial fibrillation (AF), depression, gout, and hypertension. A few days ago, he got refills for allopurinol, apixaban, lisinopril, metoprolol succinate, and sertraline. You suspect that his new prescriptions are related to coronavirus disease 2019 (COVID-19). Because you have concerns about filling these prescriptions, you reach out to DT’s provider.

After eating dinner at a friend’s wedding, JT, a healthy 37-year-old woman, develops mildly itchy, red skin on her chest and head. JT calls the pharmacy several hours later, seeking advice. You learn that JT’s meal consisted of bread, a green salad, shrimp scampi over pasta, and a glass of red wine, plus chocolate cake and coffee for dessert. JT denies having any other symptoms. Her friend suggested that she visit an emergency department for an epinephrine injection, and JT wants to know if you agree.

: The interest in hydroxychloroquine as a treatment option stems from data suggesting that it has in vitro activity against severe acute respiratory syndrome coronavirus (SARS-CoV-2).

 The recently published results of a small French study showed that hydroxychloroquine, with or without azithromycin, reduced detection of SARS-CoV-2 RNA in upper respiratory tract samples.

 The CDC cautions that further research is needed to determine what clinical benefit, if any, this treatment may have. Several medical and pharmacy organizations warn that stockpiling these medications, which are not FDA approved for COVID-19, can negatively affect patients who rely on these drugs to treat lupus and rheumatoid arthritis. Drug shortages are already anticipated because of the pandemic.

 DT’s provider should be told about the paucity of available data, especially for nonhospitalized patients, and that this drug combination poses safety concerns and can raise the risk of QTc prolongation in this patient, who has an established history of AF.

: JT’s symptoms are consistent with an allergic reaction secondary to histamine release. Both the shellfish and the wine, and possibly the chocolate cake, contain large quantities of histamine. Because JT is not experiencing severe symptoms, such as airway obstruction or hypotension, intramuscular epinephrine does not appear indicated. She be advised to buy a first- or second-generation H1 antihistamine, such as cetirizine or diphenhydramine, for treatment. If her symptoms change or worsen, she should reevaluate the need to seek urgent care.  

 is a PharmD candidate at the University of Connecticut School of Pharmacy in Storrs.

, is an associate clinical professor at the University of Connecticut School of Pharmacy in Storrs.

Yao X, Ye F, Zhang M et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 

 Published online March 9, 2020. doi:10.1093/cid/ciaa237

Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. 

 Published online March 20, 2020. doi:10.1016/j.ijantimicag.2020.105949

Lockshin MD. Hydroxychloroquine (plaquenil) and chloroquine shortage caused by COVID-19 coronavirus claims. Hospital for Special Surgery. Updated March 23, 2020. Accessed March 27, 2020. 

https://www.hss.edu/conditions_hydroxychloroquine-plaquenil-chloroquine-shortage-covid-19-coronavirus.asp

Articles

Two interactive case studies are featured. 

Interactives: Case Studies (May 2020)

JT calls to inquire about the human papillomavirus (HPV) vaccination schedule for her son CT, who just turned 17. She wants to make sure that he receives the appropriate vaccinations before heading off to college in the fall. CT received 1 dose of the HPV vaccine when he was 11 but did not get subsequent doses. JT wants to know whether her son needs to restart the series or whether he can just get another dose now.

A local physician’s assistant (PA) calls the pharmacy to ask about VB, a 19-year-old patient at his clinic who tested positive for strep throat. The PA says that his patient is allergic to penicillin, which is documented in the chart as a skin irritation that VB experienced as a child. The PA wants to prescribe cefdinir (Omnicef) and to know whether it would be safe, given this allergy.

: CT does not need to restart the series. Because he was younger than 15 years at the time of his first dose, he needs only 1 more dose to complete the 2-dose series. In a 2-dose series, the second dose is recommended 6 to 12 months after the first dose, with no maximum interval. Because CT received his first dose 6 years ago, he can receive the second dose now.

: Because the allergy is documented as a minor rash that occurred a long time ago, a third-generation (or later) cephalosporin, such as cefdinir, is appropriate to prescribe. Unlike the first- and second-generation cephalosporins, third-generation agents do not share the same R1 side chain with penicillin. It is thought that these side chains, not the β-lactam ring itself, are responsible for the cross-reactivity. Despite a low risk, the PA should counsel VB to self-monitor for any signs and symptoms of an allergic reaction and to call the office with any concerns.

Two retail pharmacy case studies are presented. 

Interactives: Case Studies (April 2020)

WR is a 45-year-old man who is initiating antiretroviral therapy for his newly diagnosed HIV infection. His past medical history includes gastritis, hypertension, and stroke, and he also has a newly diagnosed hepatitis B infection. WR's medications include amlodipine, aspirin, losartan, and omeprazole. His CD4 count is 180 cells/mm3 and the HIV viral load is 150,000 copies/mL. An HLA-B*5701 test was positive and an HIV genotype did not detect any resistance. WR has no allergies. He has been reading up on various medication regimens, as he is ready to start treatment. WR seeks the pharmacist's opinion about the fixed-combination pills Biktarvy, Odefsey, and Triumeq.

Because WR's HLA-B*5701 test was positive, regimens containing abacavir (eg. Triumeq) should be avoided to prevent severe hypersensitivity reactions. Abacavir has also been associated with cardiovascular toxicity in some studies, reaffirming its inappropriate use in this patient who has a history of stroke. WR is also actively taking the proton pump inhibitor (PPI) omeprazole. Regimens containing rilpivirine (eg. Odefsey) are contraindicated with PPIs, because rilpivirine's efficacy would be greatly reduced. Additionally, rilpivirine may have reduced efficacy in patients with high HIV viral loads (>100,000 copies/mL) and low CD4 counts (<200 cells/mm

). Of the options presented, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) would be the most appropriate for WR.

RT is a 68-year-old man who presents with new-onset, debilitating, bilateral joint pain. It has increased over the past week in intensity, causing him difficulty getting out of bed and with walking. He says that his symptoms began within days of starting 3 new medications that were prescribed by his primary care physician (PCP): amlodipine, linagliptin, and tamsulosin. No other medications were recently started, and RT denies previous drug-induced arthralgia. He self-discontinued all these medications 2 days ago and noticed some improvement in his symptoms. RT's wife encouraged him to go to the hospital because his PCP is away on vacation.

What findings should a hospital drug ingormation pharmacist share with the team?

From 2001 to 2013, the FDA received 33 case reports of severe joint pain associated with dipeptidyl peptidase-4 (DPP-4) inhibitors, including 2 cases involving linagliptin.

 Independently of its glucose-lowering effects, inhibition of the DPP-4 enzyme has been recently linked to immune-related adverse effects, including arthralgia. A recent meta-analysis of 67 randomized control trials found that DPP-4 inhibitor use is associated with a slight but significant increased risk in overall arthalgia (respiratory rate, 1.13; 95% CI, 1.04-1.22; 

 The mechanism behind the reaction is not fully understood but is believed to involve cytokine-induced inflammation. Discontinuation of the linagliptin should result in symptom resolution typically within a month.

 RT should not be rechallenged with another DPP-4 inhibitor, as arthralgia is a class effect.

Stefanie C. Nigro, PharmD, BCACP, CDE, BC-ADM,

 is an associate clinical professor at the University of Connecticut School of Pharmacy in Storrs.

FDA. FDA drug safety communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. FDA website. 

www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-dpp-4-inhibitors-type-2-diabetes-may-cause-severe-joint-pain

 Updated June 23, 2016. Accessed February 24, 2020.

Men P, He N, Song C, Zhai S. Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: a systematic review and meta-analysis [published online August 1, 2017]. 

2017;43(6):493-500. doi: 10.1016/j.diabet.2017.05.013.

What would you recommend for these patients?