Abstract
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Panic Attack Induced by Single Dose of Prednisone
A 58-year-old man was admitted to the hospital because of increasingly worsening shortness of breath upon exertion. He had a history of diabetes, obstructive sleep apnea, asthma, and chronic obstructive pulmonary disease. He had been regularly medicated with a formeterol inhaler, mometasone inhaler, montelukast, gabapentin, omeprazole, and terazosin. On an as-needed basis, he used the combination inhalation solution of albuterol and ipratropium. He had not used this medication for 48 hours before presentation to the hospital. The patient's vital signs and initial lab tests were all within normal limits.
The patient was given a single dose of prednisone 20 mg; within 30 minutes, he developed symptoms of a panic attack. He reported palpitations and chest discomfort while becoming agitated, restless, and anxious. Additionally, he became diaphoretic and complained of nausea, blurred vision, and “feelings of derealization.” His vital signs changed markedly; his pulse was 140 beats/min, blood pressure of 150/105 mm Hg, and a respiratory rate of 24 breaths/min. The patient was given 2 mg of lorazepam orally, and his vital signs and panic symptoms returned to normal within 30 minutes. He later told his physician that he had had a similar experience 4 years earlier when he was given a 60 mg dose of prednisone. At his regular visits 3 and 6 months later, there were no further signs of panic attacks.
The authors state that this may be the first report in the literature of a panic attack induced by a single dose of prednisone. The authors offer a few brief statements concerning the possible pathophysiology of such a reaction and make reference to a report that panic disorder has been associated with long-term use of corticosteroids.
Iskander JW, Wood RL, Ali R, Alemu F. Panic attack induced by a single dose of prednisone. Ann Pharmacother. 2011;45(11):1456–1457.
Intracranial Hemorrhage After High-dose Methylprednisolone
A 5-year-old girl without any prior medical problems developed acute bruising and petechiae and was taken to her pediatrician. The physical examination was normal except for the obvious bruising, and the girl's vital signs were normal. Laboratory examination revealed an “isolated thrombocytopenia.”
Her platelet count was 1 × 103 cells/mm3 (reference range for age 5, 250–550 × 103 cells/mm3). She was diagnosed with immune thrombocytopenic purpura and was “managed conservatively.”
Four days later, she developed severe epistaxis and large ecchymoses that caused her hemoglobin to fall to 5.8 g/dL (11.5–13 g/dL). She was treated with transfusions of packed red blood cells and was given a single dose of intravenous immunoglobulin (IVIG). Her platelet count was still extremely low at 2 × 103 cells/mm3. After another dose of IVIG, oral prednisone, and more transfusions, the patient's hemoglobin stabilized and the platelet count reached 21 × 103 cells/mm3. Thirty-six hours later, the girl developed “profuse mucosal bleeding from nose and mouth,” and the platelets were measured at 1 × 103 cells/mm3.
She was started on high-dose methylprednisolone (15 mg/kg) and a platelet transfusion, but she immediately developed a severe headache followed by generalized seizures. Her blood pressure had risen to 170/90 mm Hg and a stat computed tomography scan of her head showed “extensive bifrontal intracranial hemorrhage.” The girl underwent intensive care procedures with continuous platelet transfusions, but she died.
The authors suspect that the methylprednisolone caused the rise in blood pressure that may have led to the intracranial bleeding. They state that that the side effects of the accepted corticosteroid therapy may have hastened this patient's death.
Heitink-Pollé KMJ, Jan Pot D, Engelkes M, Bruin MCA. Intracranial hemorrhage after high-dose methylprednisolone in a child with acute thrombocytopenic purpura. Ann Hematol. 2011;90(11):1361–1363.
Atrial Flutter Associated with Carboplatin Administration
A 69-year-old man with a history of hypertension and an asymptomatic inferior myocardial infarction developed small cell lung cancer with widespread metastases. After radiation treatments, he was started on a chemotherapy regimen of carboplatin and etoposide infusions. He tolerated the first cycle of chemotherapy without any problems; but during his second round of treatment, he “developed a narrow complex tachycardia with a ventricular rate of 160 beats/min during the infusion of carboplatin.” He had not yet received the second etoposide dose.
Besides the tachycardia, the rest of the physical and laboratory exams were essentially normal with the exception of “a nondisplaced but bounding point of maximal cardiac impulse.” Flutter waves were observed in the jugular veins. The tachycardia worsened, and the patient became dizzy and short of breath. Rate control using diltiazem and metoprolol was hampered by the development of hypotension. As the decision was being made for some sort of cardiac intervention, the patient's heart rate returned to a sinus rhythm about 24 hours after the infusion. The patient remained in sinus rhythm 2 days later and was discharged. He died at home 8 days later of a presumed cardiac arrhythmia, but an autopsy was not performed.
The authors offer a review on the cardiotoxicity of chemotherapy agents. While the cardiac toxicity associated with the use of the anthracycline antineoplastics is well known, the authors describe toxicity caused by platinum-containing agents like cisplatin. This patient did have underlying cardiac disease, but the temporal relationship of the arrhythmia in relation to the carboplatin infusion raises the strong possibility that this adverse event may have hastened this patient's demise. Zakaria S, Lu KY, Nussenblatt V, Browner I. Atrial flutter associated with carboplatin administration. Ann Pharmacother. 2011;45(11):e59.
Hyperosmolar Hyperglycemic State Associated with Ziprasidone
A 26-year-old man with paranoid schizophrenia showed a good clinical response to risperidone therapy. Within the first 13 months of treatment with this atypical antipsychotic agent, his weight increased from 73.6 kg to 121.8 kg while his body mass index (BMI) climbed from 23 kg/m2 to 38 kg/m2. His weight reached that high plateau and did not change for the next 3 years, while his glucose tolerance became slightly impaired, with his fasting glucose levels at 120 mg/dL (80–110 mg/dL). The patient's total cholesterol had gone from 135 mg/dL to 243 mg/dL during that same time period.
The decision was made to change the patient from risperidone to ziprasidone (Geodon). The changeover was done during a 3-week period, and the patient remained fine clinically. Ten weeks after starting the ziprasidone, the patient presented to the hospital with a “diminished level of consciousness,” vomiting, and dizziness. His glucose level was 1224 mg/dL, and he was hospitalized with a diagnosis of hyperosmolar hyperglycemic state associated with type 2 diabetes mellitus. He was treated with intravenous hydration and insulin; after 72 hours, his glucose levels had returned to normal. He was discharged on oral metformin, short-acting insulin injections prior to each meal, and intermediate-acting insulin.
The ziprasidone was stopped a few weeks later, and he was then treated with haloperidol. The insulin treatments were soon stopped, and the patient continued his diabetes therapy with metformin alone.
The patient was switched from an antipsychotic agent that caused metabolic problems to a drug thought to be safer, but the new drug, ziprasidone, made this patient's glucose tolerance worse.
Létourneau G, Abdel-Baki A, Dubreucq S, Mahone M, Granger B. Hyperosmolar hyperglycemic state associated with ziprasidone treatment: a case report. J Clin Psychopharmacol. 2011;31(5):671–673.
Dress Syndrome Associated with Antibiotic Therapy
A 30-year-old man with a history of type 1 diabetes mellitus, hypertension, vascular disease, diabetic retinopathy, and stage 2 chronic renal failure developed endocarditis that necessitated aortic valve replacement surgery. Prior to the surgery, the patient's blood cultures were positive for Streptococcus dysgalactiae, and he was started on intravenous (IV) gentamicin and penicillin G. When he developed a rash to the penicillin, he was switched to IV vancomycin and the gentamicin was discontinued. Because of severe valve insufficiency, the surgery was performed before the endocarditis was eradicated.
The patient stayed on the IV vancomycin. Ten days after successful aortic valve replacement, he developed acute renal failure that required one-time hemodialysis. The patient's body temperature became elevated to 103.5°F and his white blood cell (WBC) count was 35 × 103 cells/mm3 (4.4–11.3 × 103 cells/mm3). Gentamicin and ceftriaxone were added without any benefit. A repeat echocardiogram showed “no signs of acute infectious endocarditis,” and blood cultures were negative. The patient had also developed widespread peripheral lymphadenopathy. A hematology consultant was called for suspected lymphoma; at this point, the WBC count was at 40 × 103 cells/mm3 with 24% eosinophils (0%–4%). The patient also had a “generalized pruritic rash.” Other antibiotics had been tried, but again without any positive effect.
It was finally decided that all antibiotics should be stopped as the possibility of a hypersensitivity syndrome was being considered. Topical and systemic corticosteroid therapies were initiated, and the patient showed a dramatic improvement in all symptoms. He was discharged with normal renal function, a normal eosinophil count, and “remittent lymphadenopathy.”
The diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome was made retrospectively. This diagnostic entity was first described in 1996, and this column has relayed a few of the accounts of such reactions over the past few years. The last description of such a reaction was published in February 2011, a reaction caused by clindamycin. 1
The authors tell us that vancomycin has been implicated in the DRESS syndrome in at least 5 previously published cases. Of course, this patient was subjected to multiple agents that may have possibly caused this adverse event.
Schnetzke U, Bossert T, Scholl S, Freesmeyer M, Hochhaus A, La Rosée P. Drug-induced lymphadenopathy with eosinophilia and renal failure mimicking lymphoma disease: dramatic onset of DRESS syndrome associated with antibiotic treatment. Ann Hematol. 2011;90(11):1353–1355.
Accidental Polydipsia and Hyponatremia from Diphenhydramine
A 66-year-old man with a history of benign prostatic hyperplasia (BPH) developed nasal congestion and took 3 tablets of diphenhydramine (dosage not reported). The anticholinergic effects of the diphenhydramine caused him to be unable to urinate. The patient thought that he had to “protect his kidneys,” so he decided to force fluids. He purposefully drank “an estimated 10 liters of water over the next 3 hours.” Soon after, he became confused and had 2 generalized seizures that were witnessed by a companion.
When the patient presented to the emergency department (ED), his vital signs were in the normal ranges, except for his blood pressure, which was low at 115/51 mm Hg. He was given lorazepam and levetiracetam and had no further seizure activity. Laboratory examination revealed a very low serum sodium of 116 mEq/L (135–145 mEq/L), and the serum creatinine was normal at 1 mg/dL.
A Foley catheter was inserted and 2.8 L of urine at low osmolarity were immediately returned. The patient continued to produce 10.5 L of urine, and his serum sodium came back to 131 mEq/L after a period of 5 hours. The serum sodium was normal 5 hours later. The patient's sensorium cleared, but he complained of severe muscle pain. The patient's creatine kinase level was then discovered to be 216,010 IU/L (60–400 IU/L), probably due to seizure-induced rhabdomyolysis. The patient was treated with controlled hydration, and all muscle problems resolved within 5 days.
This case is an example of the possible danger of using anticholinergic agents in patients with BPH. The psychiatric literature has seen many reports of such problems in patients receiving anticholinergic drug therapy. Almost all of the over-the-counter sleep medications contain diphenhydramine, a potent antihistamine with strong anticholinergic properties. Patients with BPH must be warned about using such sleep medications.
Pyle R, Scott M, Bartholomew J, McGrath S, Moffett B. Accidental polydipsia and hyponatremia from diphenhydramine urinary retention. Am J Med. 2011;124(10):e5–e6.
Reversible Posterior Leukoencephalopathy Syndrome (Rpls) Associated with Ustekinumab Therapy
A 65-year-old woman with plaque psoriasis had only been treated with topical steroids and acitretin during the almost 30 years that she had suffered with the skin condition. She entered a phase 3 study with an investigational agent called ustekinumab (marketed late in 2009 in the United States as Stelara), which is an inhibitor of interleukin 12 and interleukin 23. The woman received 2 initial doses 4 weeks apart and then received 1 dose every 12 weeks for 2.5 years. The drug is only administered by the subcutaneous route.
Six weeks after the patient received her 12th dose of the antipsoriatic agent, she developed nausea, vomiting, and a severe headache. Soon after, she suffered the first of 3 seizures, 2 of which were observed in the ED a few hours after the onset of symptoms. It was later reported that the woman “had experienced some episodes of head tremor over the previous 1 to 2 weeks.”
The woman was confused and disoriented in the ED, and her blood pressure was elevated to 152/92 mm Hg. She had no history of hypertension. After the second seizure in the ED, she was treated with lorazepam, phenytoin, and propofol. She was intubated for airway protection. When she later developed a fever of 102.7°F, she was empirically treated with IV acyclovir and piperacillin. All lab tests were normal, including a lumbar puncture, where the protein level was only slightly elevated but without any WBCs.
Computed tomography scans and magnetic resonance imaging of the patient's head revealed bilateral white matter changes, and the diagnosis of reversible posterior leukoencephalopathy syndrome (RPLS) was made. The patient made a rapid improvement and was extubated the following day. She remained confused for a few days, but was discharged on hospital day 6. She was continued on phenytoin for another month and made a complete recovery. The ustekinumab was discontinued.
The authors tell us that this rare adverse event happened just once in the 4,000 patients who received the drug during clinical trials. The authors discuss the supposed mechanisms of RPLS in the well-referenced discussion section. In 2007, this column reviewed RPLS caused by carboplatin 2 and linezolid. 3
Gratton D, Szapary P, Goyal K, Fakharzadeh S, Germain V, Saltiel P. Reversible posterior leukoencephalopathy syndrome in a patient treated with ustekinumab. Arch Derm. 2011;147(10):1197–1202.