You are here

P T. 2019;44(7): 416, 417-423

Amiodarone-Induced Syndrome of Inappropriate Antidiuretic Hormone: A Case Report and Review of the Literature

Gretchen P. Marcelino PharmD
Cyril Manuel C. Collantes PharmD
Jomi K. Oommen PharmD
Shan Wang BS, PharmD, BCCCP
Heather Baldassari MSPAS, PA-C
Rajanandini Muralidharan MD
Adel Hanna MD, FACC

INTRODUCTION

Amiodarone is a class III Vaughan-Williams antiarrhythmic agent but it possesses biophysical characteristics of classes I–IV. Amiodarone prolongs the myocardial action potential and refractory period by affecting the sodium, potassium, and calcium channels.1 It is used in the treatment of various cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, atrial fibrillation, and supraventricular tachycardia. The elimination half-life varies by formulation and chronicity of dosage. On average, the oral chronic-therapy elimination half-life ranges from 40 to 55 days, a single IV dose has an elimination half-life range of 9 to 36 days, and a single oral dose has an elimination half-life range of 15 to 142 days.2 The accumulation of amiodarone in various organs may lead to several adverse effects, among them pulmonary fibrosis; thyroid function abnormalities, including hyperthyroidism (3–5%) and hyperthyroidism (5–25%, from iodine in the chemical moiety3); corneal deposits; cardiac toxicity; liver function abnormalities (increases in ALT and AST); photosensitivity; and peripheral neuropathy.4

Syndrome of inappropriate antidiuretic hormone occurs when there is an excessive secretion of antidiuretic hormone (ADH) or vasopressin from the posterior pituitary gland. This leads to the reabsorption of water from the renal tubules into the circulation, manifesting as hypoosmotic euvolemic (or slightly hyper-volemic) hyponatremia and with elevated urine sodium and urine osmolality. Hypothyroidism and adrenal insufficiency can mimic SIADH’s clinical manifestations and should be excluded when making a diagnosis. Common etiologies include malignancy and neurological and pulmonary disorders.5 Medications that can cause SIADH include alkylating agents, carbamazepine, chlorpropamide, diuretics, selective serotonin reuptake inhibitors ([SSRIs], such as citalopram and escitalopram), antipsychotics (risperidone and haloperidol, usually), and pain medications (typically duloxetine and pregabalin).5,6

Amiodarone-induced SIADH has been sporadically reported in the literature.720 We discuss a case that occurred following nine months of amiodarone therapy and upon rechallenge at discharge.

CASE REPORT

An 88-year-old Caucasian male presented to the emergency department for trauma after falling backward down the stairs. His chief complaint was back pain, with no reported loss of consciousness. He was neurologically intact and his Glasgow coma scale (GCS) score was 15. He was in normal sinus rhythm, with a heart rate (HR) of 59 beats per minute (bpm), a blood pressure reading of 90/60 mmHg, and a respiratory rate of 20 breaths per minute. His temperature was 36.1°C, and his oxygen saturation was 100% on room air.

The patient’s medical history was significant for hypertension, paroxysmal atrial fibrillation, emphysema, myocardial infarction, benign prostatic hyperplasia, chronic kidney disease, Meniere’s disease, anemia, and gastroesophageal reflux. His surgical history included an aortic valve replacement one year earlier. He had been on amiodarone (Cordarone®) 200 mg once daily for nine months for atrial fibrillation. In addition, he had been taking aspirin 81 mg daily; metoprolol succinate (Toprol XL®) 50 mg once daily; omeprazole (Prilosec®) 20 mg once daily; tiotropium bromide (Spiriva® Handihaler®) 18 mcg inhaled daily; budesonide/formoterol fumarate dihydrate (Symbicort®) 160/4.5 mcg, two puffs twice daily; cetirizine (Zyrtec®) 10 mg daily, as needed; docusate sodium (Colace®) 100 mg three times daily, as needed; polyethylene glycol 3350 (Miralax®) 17 gm daily, as needed; ferrous sulfate 325 mg daily; finaste-ride (Proscar®) 5 mg daily; tamsulosin hydrochloride (Flomax®) 0.4 mg daily; and vitamin C 500 mg daily.

Our patient denied any recent history of vomiting, diarrhea, polydipsia, and/or decreased oral intake. His physical examination showed no visible injuries to the head or neck. He was in normal sinus rhythm, and his lungs were clear to auscultation. His orthostatics were within normal limits, and his heart and lung ultrasound results were all within normal limits. His skin turgor and mucous membranes were also normal. There was no jugular venous distention, and no edema was noted in his lower extremities. A computed tomography (CT) scan of his head and lumbar spine was negative. A CT scan of his cervical spine showed a C4 extension teardrop fracture, and a CT scan of his abdomen and pelvis showed an active arterial extravasation into the left gluteal region and a right ninth rib fracture. Table 1 shows the laboratory values upon admission, and Figure 1 illustrates the trending sodium levels.

Euvolemia was confirmed through orthostatic and ultrasound findings of the inferior vena cava. Thyroid-stimulating hormone (TSH) levels and cortisol levels were within normal limits, ruling out hypothyroidism and adrenal insufficiency as a cause of our patient’s SIADH. His high urinary sodium level (> 20 mEq/L) and urinary osmolality (> 100 mOsm/kg) led to the SIADH diagnosis.21 He was not taking any other medication that may have contributed to the etiology of SIADH, and he had no history of human immunodeficiency virus (HIV) infection, malignancies, or pneumonia.

Amiodarone and metoprolol were held because of bradycardia (59 bpm) and hypotension (90/60 mmHg), which were secondary to acute bleeding. In the setting of hypotension and a declining hemoglobin (7.4 g/dL), hematocrit (30.5%), and thrombocytopenia (158 K/uL), the patient underwent angioembolization for arterial extravasation into the left gluteal region. He was transferred to the surgical intensive care unit for hemodynamic monitoring and a blood transfusion. After two units of packed red blood cells and platelets were administered, his blood pressure normalized. Thromboelastography (TEG)––a hemostatic assay that measures properties of whole-blood clot formation––showed platelet dysfunction, indicating increased platelet inhibition, which was likely a result of the aspirin. The aspirin was held on admission because of active hemorrhaging. In an attempt to reverse platelet dysfunction, platelets and desmopressin were administered. Desmopressin is known to increase von Willebrand factor, which can increase platelet aggregation.22

Approximately two hours after admission, our patient experienced a tonic-clonic seizure lasting about one minute. He was treated with IV levetiracetam 500 mg twice daily and monitored on a video electroencephalogram (VEEG) on Days 2 and 3 of admission; no further seizures were noted. We did not determine a cause for the seizure, but it could have been a result of a concussion or fall, or the rapid decrease in serum sodium to 123 mEq/L. Generally, it is rare to observe seizures at such a level.23

Fluid restriction (500–800 mL/day) and the close monitoring of sodium levels were performed every two hours. Within 19 hours, his serum sodium levels had improved from 123 mEq/L (Day 1) to 130 mEq/L (Day 4). The average sodium correction rate was 0.37 mEq/hour, which is consistent with recommendations to keep it at < 10 mEq/24 hours.24

On Day 4, the patient was rechallenged with amiodarone 200 mg once daily for the treatment of atrial fibrillation. His serum sodium levels remained unchanged. On Day 6, he was transferred to the surgical step-down unit, then discharged on Day 7 to a subacute rehabilitation facility.

Two months after his discharge, our patient remained adherent on amiodarone. His serum sodium level ranged from 126 mEq/L to 131 mEq/L over a two-week period post-discharge. Since his hospitalization, he has been supplemented with sodium chloride tablets 1 g twice daily and has remained stable.

DISCUSSION

The Naranjo scale was used to determine the likelihood of amiodarone being the cause of an adverse drug reaction. A review of the literature shows that amiodarone-induced SIADH has been reported in numerous articles (references 720 in Table 3). Our patient had been on amiodarone for nine months prior to his admission. His serum sodium level improved over the course of admission: before rechallenge, his level was 130 mEq/L, and two months after rechallenge, the level had declined to 126 mEq/L. All other contributors to the presentation of SIADH could not be ruled out. Our patient was not given placebo during his hospital stay, his amiodarone concentrations were never measured, and his dosage was neither increased nor decreased. It is not known whether he experienced SIADH during his previous exposure to amiodarone. Syndrome of inappropriate antidiuretic hormone was confirmed by serum sodium, urine sodium, and urine osmolality. The calculated Naranjo score was 9, which we determined to be a definite adverse drug reaction (Table 3).

The majority of reported cases of SIADH related to amiodarone have been seen in elderly male patients (18/22 reports, [81.8%]) aged between 62 and 88 years (Table 2). In the cases we reviewed, most patients had a medical history of hypertension, hyperlipidemia, congestive heart failure, and arrhythmia. The duration of amiodarone therapy varied from less than 24 hours to five years. There was a broad spectrum of side effects, including altered mental status, torsades de pointes, dizziness, hypotension, generalized weakness, loss of appetite, and hyponatremia. Adrenal insufficiency was ruled out in all cases. There were no reported seizures in patients among the cases we reviewed. In the setting of hyponatremia, amiodarone was either held, discontinued, or dose-adjusted. Patients were managed with normal saline, 3% hypertonic saline, demeclocycline (an ADH antagonist in the renal collecting tubule), fluid restriction, and/or tolvaptan (a vasopressin receptor antagonist). Sodium levels also were closely monitored. Patients’ recovery time varied from one day to one month.720

Amiodarone has been identified as the cause of otherwise unexplained SIADH in several cases. One of the earliest observations was reported by Odeh et al. in an elderly woman who was taking amiodarone 300 mg daily for six months for paroxysmal atrial fibrillation. She presented with hyponatremia with a serum sodium level of 120 mmol/L, and mild generalized weakness, chest pain, and palpitations. After fluid restriction and discontinuing amiodarone, her serum sodium normalized within 14 days.7

Following our review of all available literature, we could make no correlation between dosage of amiodarone, duration of treatment, and serum sodium concentration. For example, when comparing duration of amiodarone therapy, we noted that hyponatremia onset presented within as quickly as two days, as reported by Aslam et al. (serum sodium level, 117 mmol/L) and Afshinnia et al. (serum sodium level, 116 mmol/L).10,15 However, the longest time to onset, reported by Maloberti et al., presented after five years of maintenance therapy with amiodarone 200 mg daily (serum sodium level, 117 mEq/L).13 When we compared serum sodium levels, the lowest on presentation was 105 mmol/L after 18 days of amiodarone therapy (Pham et al.).17 The highest level on presentation was 134 mmol/L after 10 to 12 days of therapy (Shah et al).19 Recovery time after discontinuing amiodarone varied. Dutta et al. and Iovino et al. presented the shortest recovery time: hyponatremia resolved within three days after amiodarone discontinuation.8,16 The longest recorded recovery period was up to four weeks, as reported by Ikegami et al. and Patel et al.12,14 (Table 1).

Among the cases, the dose and administration route of amiodarone varied. Afshinnia et al. and Oner et al. reported hyponatremia after an IV bolus over 30 minutes (150 mg and 300 mg, respectively), followed by a continuous IV infusion over 24 hours (900 mg and 1,050 mg, respectively).10,11 Hyponatremia symptoms such as altered mental status and generalized fatigue were seen at Days 2 to 3 of therapy. In both cases, fluids were restricted and amiodarone was discontinued. Ikegami et al. reported on two elderly males who had hyponatremia after an oral loading dose of amiodarone 800 mg daily for seven days, 200 mg for seven days, then 100 mg daily for another eight days. Hyponatremia resolved upon initiation of maintenance therapy, decreasing the dose to 100 mg in both cases, suggesting a dose-dependent phenomenon.12

Amiodarone-induced SIADH has been reported in a number of patients who received chronic amiodarone therapy. Maloberti et al. reported on a 78-year-old man taking amiodarone 200 mg daily for five years who presented with SIADH, as well as hypoosmotic hypochloremic hyponatremia (serum sodium level, 110 mEq/L) and transaminitis. As with previous cases, the amiodarone was discontinued and his fluids were restricted. His serum sodium levels resolved after six days, and his liver enzymes decreased gradually over one to two months.13 Of note, our patient has been on chronic amiodarone maintenance therapy for nine months.

In most of the published cases,714,1620 the amiodarone dose was either lowered or discontinued, and patients typically were not rechallenged. However, Aslam et al. reported a case of an unintentional rechallenge, in which a 72-year-old male was initiated on amiodarone due to refractory ventricular tachycardia. His serum sodium level dropped to 117 mmol/mL 48 hours after he had received an oral loading dose of 10 g over five days. When he was transitioned to a 200-mg daily maintenance dose, his serum sodium level began to increase 48 hours later, then stabilized in 14 days. Because of other complications (e.g., fever, leukocytosis, and methicillin-susceptible Staphylococcus aureus bacteremia) in his treatment, the amiodarone had to be reloaded. Immediately, his serum sodium level decreased to 121 mmol/mL, then increased after he resumed the maintenance dosing.15 Similarly, the discontinuation of amiodarone 200 mg daily and restriction of fluid led to our patient’s serum sodium level increasing to 130 mEq/L within 19 hours. He was rechallenged with the same initial dose of 200 mg daily; subsequently, his serum sodium level decreased to 126 mEq/L within two months.

Sodium chloride tablets were initiated in our patient post-discharge at a subacute rehabilitation facility. The dose he received was 1 g twice daily, which does not correlate to the 50 mL/hr IV normal saline he was receiving as an inpatient at our facility. Syndrome of inappropriate antidiuretic hormone secretion would not be expected to respond to sodium chloride tablets, but they may be recommended in patients with severe, symptomatic, or resistant hyponatremia.21

Shortly after admission, our patient had a seizure with a serum sodium level of 123 mEq/L. No other cases of amiodarone-induced SIADH have reported seizures. Interestingly, seizures associated with hyponatremia are more likely to occur with serum sodium levels of 110 to 115 mEq/L, and it is rare to observe them at levels above 120 mEq/L.25

Medications that can cause SIADH include alkylating agents, carbamazepine, chlorpropamide, diuretics, SSRIs, antipsychotics, and pain medications. Risk factors for drug-induced SIADH include taking any of the above drugs as monotherapy or in combination; excessive fluid intake; and other underlying conditions that limit the free excretion of water.5,6 Amiodarone could cause SIADH as a result of increased secretion of arginine vasopressin relative to plasma osmolality; inherited mutations of the aquaretic vasopressin receptor; or alteration in the voltage-gated channels in neural or renal tissues.8 Some cases of carbamazepine-induced SIADH have reported increases in vasopressin levels, whereas other cases report a decrease in vasopressin, which suggests a renal effect.26 The effect of amiodarone on cardiac fibers is unknown, but the drug may be linked to autonomic dysfunction. Evidence has been found of altered osmoreceptor response, which would cause a new, lower threshold of the osmoregulatory system. Furthermore, the afferent neuropathy of osmolarity and cardiac volume receptors has been proposed, and with this, tubular sensitivity to ADH may also increase.27 In Guillain-Barré syndrome (GBS), SIADH has been noted as a result of autonomic dysfunction-induced SIADH (4.8–15% of patients in the studies);28 however, the mechanism of SIADH in GBS is not completely understood.

CONCLUSION

Amiodarone is useful in treating cardiac arrhythmias, but may be toxic to different organ systems. It may cause acute or chronic SIADH, which can occur with any formulation of amiodarone and apparently in a dose-dependent manner. The mechanism of amiodarone-induced SIADH is unknown. Seizures have not been reported in previous literature. Sodium levels usually stabilize within two weeks with continued maintenance-dose treatment.

Although SIADH is an infrequent consequence of amiodarone therapy, the case we present supports the close laboratory monitoring of electrolytes throughout treatment. Clinicians should be aware of this rare but serious adverse drug reaction related to amiodarone, and monitor their patients accordingly.

Figure and Tables

Serum Sodium Levels Throughout Course of Admission

Summary of Literature on Amiodarone-Induced SIADH

ARTICLE INFORMATION PATIENT INFORMATION AMIODARONE ADVERSE REACTION MANAGEMENT
Year Author Origin Sex Age Comorbidities Therapy Duration Serum Sodium on Presentation* Description Treatment Recovery Time to Normalization Rechallenge
2011 Afshinnia10 North America M 66 HTN, HLD, CAD, CHF LD IV 150 mg; continuous infusion 900 mg/24 hrs, then 400 mg PO t.i.d. x 1 week 2 days 116 mmol/L hyponatremia d/c amiodarone Day 7 16 days No
2004 Aslam15 North America M 72 CHF, VT, PAF 2,000 mg QD for 5 days (10 g), then 200 mg QD 2 days 117 mmol/L hyponatremia, clinically euvolemic lowered dose to 200 mg QD (maintenance dose) 14 days Yes
2004 Aslam15 North America (rechallenge) M 72 CHF, VT, PAF 1,666.67 mg QD for 6 days (10 g), then 200 mg QD < 24 hours 121 mmol/L hyponatremia lowered dose to 200 mg QD (maintenance dose) < 24 hours N/A
2005 Dan9 Romania (case series of 7 patients) All M mean 77 not specified mean dose, 277 mg QD mean, 18 ± 12 months 118.12 mEq/L urine sodium concentration > 40 mEq/L, hyponatremia, neurological symptoms; 3 of 7 patients had TdP fluid restriction; amiodarone d/c in 3 of 7 patients due to TdP; lowered dose in 1 of 7 patients mean, 2.5 weeks No
2014 Dutta8 India M 63 hypothyroidism, chronic bronchitis, HTN, VT, BPH 100 mg QD 8 months 109 mmol/L low plasma osmolality, hyponatremia, increased urine sodium fluid restriction; 10–15 g of added salt QD; tolvaptan; d/c amiodarone 3 days No
2002 Ikegami12 Japan M 63 CHF, VT 800 mg QD 7 days 119 mmol/L general malaise, hyponatremia lowered dose to 100 mg QD; fluid restriction 3–4 weeks No
2002 Ikegami12 Japan M 87 CHF, VT 200 mg QD for 7 days, then 100 mg QD 15 days 121 mmol/L loss of appetite, general malaise, hyponatremia continuous 100 mg QD; moderate fluid restriction (800 mL/d) 2 weeks No
2014 Iovino16 North America M 68 DM, HTN IV 1,050 mg/24 hrs, then 200 mg PO once daily 10 days 122 mmol/L headache, muscle soreness, falls, unsteadiness, attention impairment 3% NaCl; fluid restriction; d/c amiodarone 3 days No
2014 Iovino16 North America M 72 HTN, HLD IV 1,050 mg/24 hrs, then 200 mg PO once daily 12 days 125 mmol/L headache, muscle soreness, falls, unsteadiness, attention impairment 3% NaCl; fluid restriction; d/c amiodarone 3 days No
2014 Jiansakul18 North America M 67 HTN, atrial flutter, alcohol use disorder unknown 2 months 118 mmol/L hypothyroidism, hyponatremia, sudden-onset dizziness, weakness, change in mental status fluid restriction; levothyroxine; demeclocycline; d/c amiodarone not specified No
2015 Maloberti13 Italy M 78 STEMI, CHF, VT 200 mg once daily 5 years 110 mEq/L hypoosmotic hypochloremic hyponatremia, transaminitis 3% NaCl; fluid restriction; d/c amiodarone 6 days No
1999 Odeh7 Israel F 62 PAF, HTN, peptic disease 300 mg QD 6 months 120 mmol/L hyponatremia, hypertension, irregular heartbeat/palpitations, chest pain, mild generalized weakness fluid restriction; d/c amiodarone (switched to prajmalium) 14 days No
2015 Oner11 Turkey F 88 HTN, HLD LD IV 300 mg in 30 min for total dose of 1,050 mg in 24 hrs, then 200 mg PO QD 3 days 111 mmol/L altered mental status, weakness, loss of appetite, drowsiness, hypoosmotic hyponatremia fluid restriction; 3% hypertonic saline; d/c amiodarone; furosemide low dose 3 days No
2002 Patel14 USA M 67 COPD, CAD, CHF, VT, diverticulosis 200 mg once daily 3 months 117 mEq/L hypoosmotic hyponatremia fluid restriction; d/c amiodarone 4 weeks No
2013 Pham17 North America M 84 HTN, DM, NSTEMI LD IV 150 mg, then continuous infusion 1 mg/min; after 24 hrs, IV switched to PO 400 mg Q8H, then tapered over 7 days to 400 mg QD 18 days 105 mmol/L altered mental status, weakness, loss of appetite, drowsiness, hypoosmotic hyponatremia 3% hypertonic saline; demeclocycline; fluid restriction 10 days No
2008 Paydas20 Turkey M 58 HTN not specified not specified 107 mEq/L hyponatremia, high urinary osmolarity, asymptomatic d/c amiodarone 2 weeks No
2013 Shah19 North America F 67 HTN, PAF IV 150 mg, then 900 mg/24 hrs, then 200 mg t.i.d. 10–12 days 134 mmol/L hyponatremia, hypotension, clinically euvolemic d/c amiodarone 7 days No

Key: BPH = benign prostatic hyperplasia; b.i.d. = twice daily dosing; CAD = coronary artery disease; CHF = chronic/congestive heart failure; COPD = chronic obstructive pulmonary disease; d/c = discontinued; DM = diabetes mellitus; F = female; HLD = hyperlipidemia; hrs = hours; HTN = hypertension; IV = intravenous; LD = loading dose; M = male; min = minute; NaCl = sodium chloride; NSTEMI = non–ST-elevation myocardial infarction; PAF = paroxysmal atrial fibrillation; PO = oral administration; QD = daily dosing; Q8H = every 8 hours; STEMI = ST-elevation myocardial infarction; TdP = torsade de pointes; t.i.d. = three times a day; VT = ventricular tachyarrhythmia

*Serum sodium level on presentation represents value as reported by authors; therefore, units vary by individual practice sites: 1 mEq/L sodium = 1 mmol/L sodium.

Patient’s Laboratory Findings on Admission

Laboratory Parameter Lab Value Reference Range
Initial serum sodium level (see subsequent levels in Table 3) 123 mEq/L 135–145 mEq/L
Serum osmolality 179 mOsm/L 274–316 mOsm/L
Glucose level 101 mg/dL 70–126 mg/dL
Anion gap 1 mEq/L 7–16 mEq/L
Phosphate 2.0 mg/dL 2.7–4.7 mg/dL
Urine specific gravity 1.034 1.003–1.035
Urine sodium 65 mEq/L < 30 mEq/L
Urine osmolality 499 mOsm/kg 500–800 mOsm/kg
Serum cortisol 27.7 mcg/dL
Uric acid 3.4 mg/dL 2.9–8.3 mg/dL
Thyroid stimulating hormone (TSH) 2.021 μIU/mL 0.36–5.8 μIU/mL
Serum creatinine 1.6 mg/dL baseline 1.7 mg/dL
Blood urea nitrogen (BUN) 27 mg/dL 6–20 mg/dL
Glomerular filtration rate (GFR) 35.3 mL/min/1.73 m2 90–120 mL/min/1.73 m2
Red blood cell (RBC) 2.6 M/μL 4–6 M/μL
Hemoglobin (Hgb) 7.4 g/dL 12–18 g/dL
Hematocrit (Hct) 30.5% 38–52%
Platelet (Plt) 158 K/μL 160–392 K/μL

Naranjo Adverse Drug-Reaction Probability Scale

QUESTION YES NO UNKNOWN SCORE DESCRIPTION
1. Are there previous conclusive reports on this reaction? +1 0 0 YES Amiodarone-induced SIADH has been reported.720
2. Did adverse event appear after suspected drug was given? +2 −1 0 YES
2
Patient was on amiodarone for 9 months prior to admission.
3. Did adverse reaction improve when drug was discontinued/specific antagonist given? +1 0 0 YES
1
Serum sodium level improved over course of admission.
4. Did adverse reaction appear when drug was readministered? +2 −1 0 YES
2
Serum sodium level before rechallenge: 130 mEq/L. Serum sodium level 2 months after rechallenge: 126 mEq/L.
5. Could reaction have occurred through alternative causes? −1 +2 0 No
2
Alternative causes/contributors ruled out.
6. Did reaction reappear when placebo was given? −1 +1 0 UNKNOWN
0
Placebo was not given.
7. Was drug detected in any body fluid in toxic concentrations? +1 0 0 UNKNOWN
0
Amiodarone concentrations were never measured.
8. Was reaction more severe when dose was increased/less severe when dose was decreased? +1 0 0 NO
0
Amiodarone dosage was neither increased nor decreased.
9. Did patient have similar reaction to same/ similar drug in any previous exposure? +1 0 0 UNKNOWN
0
Not known if patient experienced SIADH during previous amiodarone exposure.
10. Was adverse event confirmed by any objective evidence? +1 0 0 YES
1
SIADH confirmed by serum sodium, urine sodium, and urine osmolality.
TOTAL SCORE 9

SCORING

≥ 9 = definite ADR; 5–8 = probable ADR; 1–4 = possible ADR; 0 = doubtful ADR

Author bio: 
Drs. Marcelino, Collantes, and Oommen were PGY-1 Pharmacy Practice Residents at NYU Winthrop Hospital in Mineola, New York at the time of writing. Dr. Wang is a Critical Care Clinical Pharmacist and Pharmacy Residency Program Director at NYU Winthrop Hospital; Ms. Baldassari is a Physician’s Assistant in the surgical ICU at NYU Winthrop. Dr. Muralidharan, Attending Physician in NYU Winthrop’s neurosurgical unit, and Dr. Hanna, Attending Physician in the surgical intensive care unit, both served as mentors.

References

  1. Vaughan Williams EM. Classifying antiarrhythmic actions: by facts or speculation. J Clin Pharmacol 1992;32;(11):964–977.
  2. Cordarone® (amiodarone) prescribing information Philadelphia, Pennsylvania: Wyeth Pharmaceuticals Inc. 2018; Available at: http://labeling.pfizer.com/showlabeling.aspx?id=93. Accessed May 20, 2019
  3. Batcher EL, Tang XC, Singh BN, et al. Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation. Am J Med 2007;120;(10):880–885.10.1016/j.amjmed.2007.04.022
  4. Goldschlager N, Epstein AE, Naccarelli G, et al. Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med 2000;160;(12):1741–1748.
  5. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders 5th edNew York, New York: McGraw-Hill. 2001;703
  6. Shepshelovich D, Schechter A, Calvarysky B, et al. Medication-induced SIADH: distribution and characterization according to medication class [published online March 2, 2017]. Br J Clin Pharmacol 2017;83;(8):1801–1807.10.1111/bcp.13256
  7. Odeh M, Schiff E, Oliven A. Hyponatremia during therapy with amiodarone. Arch Intern Med 1999;159;(21):2599–2600.
  8. Dutta P, Parthan G, Aggarwal A, et al. Amiodarone induced hyponatremia masquerading as syndrome of inappropriate antidiuretic hormone secretion by anaplastic carcinoma of prostate [published online April 8, 2014]. Case Rep Urol 2014;2014: 136984 10.1155/2014/136984
  9. Dan GA, Dan AR, Buzea A, et al. Hyponatremia—an overlooked complication of long-term amiodarone therapy. Heart Rhythm 2005;2;(suppl 5):S326–S327.10.1016/j.hrthm.2005.02.1028
  10. Afshinnia F, Sheth N, Perlman R. Syndrome of inappropriate antidiuretic hormone in association with amiodarone therapy: a case report and review of literature [published online March 23, 2011]. Ren Fail 2011;33;(4):456–458.10.3109/0886022X.2011.565138
  11. Oner O, Erdem Soyaltin U, Akar H, et al. Amiodarone-induced hyponatremia in an elderly patient. European Geriatric Medicine 2015;6;(5):476–477.10.1016/j.eurger.2015.03.009
  12. Ikegami H, Shiga T, Tsushima T, et al. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by amiodarone: a report on two cases. J Cardiovasc Pharmacol Ther 2002;7;(1):25–28.10.1177/107424840200700i104
  13. Maloberti A, Volpe M, Bombelli M, et al. Amiodarone induced SIADH: a case of rare and late onset side effects. Acta Endo (Buc) 2015;11;(4):507–511.10.4183/aeb.2015.507
  14. Patel GP, Kasiar JB. Syndrome of inappropriate antidiuretic hormone-induced hyponatremia associated with amiodarone. Pharmacotherapy 2002;22;(5):649–651.
  15. Aslam MK, Gnaim C, Kutnick J, et al. Syndrome of inappropriate antidiuretic hormone secretion induced by amiodarone therapy. Pacing Clin Electrophysiol 2004;27;(6 Pt 1):831–832.10.1111/j.1540-8159.2004.00541.x
  16. Iovino M, Iovine N, Petrosino A, et al. Amiodarone-induced SIADH: two cases report. Endocr Metab Immune Disord Drug Targets 2014;14;(2):123–125.
  17. Pham L, Shaer AJ, Marnejon T. Hyponatremia––a rare but serious complication of amiodarone: a case report and review of the literature. Case Rep Nephrol Urol 2013;3;(1):46–50.10.1159/00035091
  18. Jiansakul T, Naber T. Acute on chronic hyponatremia due to amiodarone induced hypothyroidism in a patient with chronic syndrome of inappropriate antidiuretic hormone (SIADH). Am J Kidney Dis 2014;63;(5):B6010.1053/j.ajkd.2014.01.184
  19. Shah S, Bhatnagar J. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced with amiodarone. Am J Kidney Dis 2013;61;(4):B8810.1053/j.ajkd.2013.02.296
  20. Paydas S, Araz F, Balal M. SIADH induced by amiodarone in a patient with heart failure. Int J Clin Pract 2008;62;(2):33710.1111/j.1742-1241.2006.00928.x
  21. Verbalis JG, Greenberg A, Burst V, et al. Diagnosing and treating the syndrome of inappropriate antidiuretic hormone secretion. Am J Med 2016;129;(5):537.e9–537.e23.10.1016/j.amjmed.2015.11.00
  22. DiMichele DM, Hathaway WE. Use of DDAVP in inherited and acquired platelet dysfunction. Am J Hematol 1990;33;(1):39–45.
  23. Halawa I, Andersson T, Tomson T. Hyponatremia and risk of seizures: a retrospective cross-sectional study [published online January 26, 2011]. Epilepsia 2011;52;(2):410–413.10.1111/j.1528-1167.2010.02939.x
  24. Braun MM, Barstow CH, Pyzocha NJ. Diagnosis and management of sodium disorders: hyponatremia and hypernatremia. Am Fam Physician 2015;91;(5):299–307.
  25. Nardone R, Brigo F, Trinka E. Acute symptomatic seizures caused by electrolyte disturbances. J Clin Neurol 2016;12;(1):21–33.10.3988/jcn.2016.12.1.21
  26. van der Lubbe N, Thompson CJ, Zietse R, Hoorn EJ. The clinical challenge of SIADH––three cases. NDT Plus 2009;2;(suppl 3):iii20–iii24.10.1093/ndtplus/sfp15
  27. Hoffmann O, Reuter U, Schielke E, Weber JR. SIADH as the first symptom of Guillain-Barré syndrome. Neurology 1999;53;(6):136510.1212/wnl.53.6.1365-a
  28. Anandan C, Khuder SA, Koffman BM. Prevalence of autonomic dysfunction in hospitalized patients with Guillain-Barré syndrome [published online March 23, 2017]. Muscle Nerve 2017;56;(2):331–333.10.1002/mus.25551