Esomeprazole induced Hypoglycemia

K. Abirami1, Bini Susan Isaac2

1Deputy Medical Administrator, Kauvery Hospital, Salem

2Clinical Pharmacist, Kauvery Hospital, Salem

Abstract

Esomeprazole, the (S) – isomer of omeprazole, is the first proton pump inhibitor (PPI) developed as a single isomer for the treatment of acid-peptic disease by specific inhibition of H+ K+- ATPase in gastric parietal cells.

Keywords: Hypoglycemia, Whipples triad, Glucagon

Background

Hypoglycemia is a clinical syndrome with diverse causes in which low plasma glucose concentrations lead to symptoms and signs and there is the resolution of the symptoms/signs when plasma concentration is raised.

Whipples Triad: Diagnosis of hypoglycemia requires fulfilment of Whipples Triad

  1. Signs and symptoms consistent with hypoglycemia
  2. Associated with low glucose level
  3. Relief of symptoms with supplemental glucose

Response to hypoglycemia in normal subjects

As plasma glucose levels decline within the physiologic range in the fasting state, pancreatic beta-cell insulin secretion decreases thereby increasing hepatic glycogenesis and gluconeogenesis. Low insulin levels also reduce glucose utilization in peripheral tissues inducing lipolysis and proteolysis thereby releasing gluconeogenic precursors. Thus, a decrease in insulin secretion is the first defence against hypoglycemia.

As plasma glucose levels decline just below the physiologic range counter-regulatory hormones are released. Among these pancreatic alpha-cell glucagon which stimulates hepatic glycogenolysis plays a primary role. Glucagon is the second defense against hypoglycemia.

Adrenomedullary Epinephrine which stimulates hepatic glycogenolysis and gluconeogenesis, renal gluconeogenesis is not normally critical. Epinephrine has similar hepatic effects as glucagon. It also increases the delivery of gluconeogenic substrates from the periphery inhibits glucose utilization by several tissues and inhibits insulin secretion. As with glucagon, a normally functioning liver is necessary for an adequate response. Epinephrine is the third defense against hypoglycemia. When hypoglycemia is prolonged beyond 4 h, cortisol and growth hormone also support glucose production and limit glucose utilization. As plasma glucose levels fall to lower levels, symptoms prompt the behavioral defense against hypoglycemia including the ingestion of food.

Classification of hypoglycemia

In Diabetes Mellitus, hypoglycemia is classified as

  1. Severe Hypoglycemia
  2. Documented symptomatic hypoglycemia
  3. Probable symptomatic hypoglycemia
  4. Asymptomatic hypoglycemia
  5. Relative hypoglycemia

Without Diabetes Mellitus, hypoglycemia is classified as

  1. Postprandial/Reactive
  2. Fasting/Non-reactive

Symptoms and signs of hypoglycemia

Autonomic symptoms: Recognized at a threshold of approximately 60 mg/dl

Neuroglycopenic symptoms: Occurs at a threshold of approximately 50 mg/dl

Signs of hypoglycemia

Diaphoresis, Pallor. Increased heart rate and systolic blood pressure

Signs/Symptoms/Physical Exam

General: Confusion, lethargy

HEENT: Diplopia

CVS: Tachycardia

Neurologic: Weakness, seizure

Mental Status: Irritability, short-term memory less

Skin: Pale, diaphoresis

Esomeprazole

Brand name: Inj. Esoz

Dose: 40 mg

Manufacture: Neon Laboratories Limited

Batch No: 1911039

Mechanism of Action: Works by binding irreversibly to the H+/K+ ATPase in the proton pump

Indications: GERD, Peptic Ulcer, Zollinger-Ellison Syndrome, Severe Peptic Ulcer bleeding.

Pharmacokinetics

Absorption: Oral

Distribution: 16 L

Metabolism: Liver

Excretion: Urine

Half-Life: 1-1.5 h


S.No



IP NO/UHID



AGE



GENDER



PRIMARY CONSULTANT



DIAGNOSIS



CO- MORBIDITY



INJECTION/INFUSION



STARTING DATE



STOPPING DATE



ANTIBIOTIC



DEXTROSE 25 %



STATUS

1



15377/56071



39



M



SRK



DCLD/UGI Bleed



DCLD



Injection



16-08-2021



18-08-2021



Meropenam, Metro, Levoflox



YES



ALIVE

2



15307/68994



29



F



SRK



Hypoglycemia/IDA



BA



Infusion 



06-08-2021



09-08-2021



Magnex forte



YES



ALIVE

3



15103/57680



73



F



KA



DM/CKD/HTN/CA



DM/HTN/CA



Injection



25-07-2021



28-07-2021



Minocycline



YES



ALIVE

4



14929/45764



72



F



KA



DM/HTN/Hypoglycemia



DM, CKD, PTB, PAH



Injection



12-07-2021



24-07-2021



Piptaz, Meropenam



YES



ALIVE

5



14825/30671



71



F



MVR



Post Covid, UTI, Dyselectrolymia



DM.HTN



Injection, Infusion



07-07-2021



21-07-2021



Magnex forte



YES



ALIVE

6



15151/68153



55



M



KA



Recurrent Hypoglycemia/Sepsis



DM



Injection



28-07-2021



05-08-2021



Magnex forte,clindamycin,linezolid,



YES



ALIVE

7



14923/52027



55



M



MRJ



CAD/AWMI



MI



Injection



13-07-2021



15-07-2021



Nil



YES



ALIVE

8



15443/69554`



65



F



KA



DM/HTN/CKD



DM, HTN, CKD



Injection



18-08-2021



20-08-2021



Meropenam/Clindamycin



YES



ALIVE

9



15521/14267



33



F



MRJ



Hypoglycemia, hyperinsulinemia



MCTD, PAH



Injection



20-08-2021



23-08-2021



Nil



YES



ALIVE

10



14811/65661



67



M



SRK



Periampullary Carcinoma



DM



Injection



31-07-2021



03-08-2021



Tigecycline, Colistin, Meropenam, Linezolid



YES



ALIVE

11



15117/67620



65



M



SRK



Recurrent UGI Bleed



Nil



Injection



25-07-2021



28-05-2021



Taxim, Adwift



YES



AMA

12



15128/67915



78



F



SRK



Upper GI Bleed



Nil



Infusion



26-07-2021



28-07-2021



Adwift



YES



AMA

Discussion

The index patient was a known case of DM/CKD with post-TB bronchitis admitted with gastritis. She developed recurrent hypoglycemia on 7th day of admission requiring continuous 25 % Glucose infusion (19th July). Her LFT was normal. Renal function stable. During hypoglycemia she was found to have high insulin levels. We suspected auto-immune phenomenon with insulin antibodies. We started her on hydrocortisone and then sugar levels were corrected. Her insulin antibodies came back normal. There were 3 other patients with similar issues within the 3-week period and all of them responded to short term steroids. All of them are women. All of them had documented high insulin levels during hypoglycemia. During the same time, there were 2 other patients with hypoglycemia for whom insulin levels were low. They had hypoglycemia secondary to CLD and post-OP ileus. So, the issue was not with the lab. The only common thread in all these patients was the use of esomeprazole IV infusion. The last patient was a case of acute on CKD due to IRGN. She developed gastritis due to steroids and we started her on esomeprazole IV. She immediately went into hypoglycemia which responded to stopping of esomeprazole IV and switching to pantaprazole. Diabetic chart attached below. Also at discharge 2 patients got T.nexpro and during follow up no issue. All these patients received esomeprazole brand ESCEROL by neon with batch no.1911039. This batch was introduced in Salem on 7thJuly. We had returned this product and buy Injection Nexpro. Later Voluntary Recall of product Nexpro IV Injections Batches No.K676H001 to K676H008 was carried out by Torrent Pharmaceuticals as a part of ongoing quality assurance checking.

Esomeprazole induced Hypoglycemia1
Esomeprazole induced Hypoglycemia2

Conclusion

All patients developed hypoglycemia after admission, especially during the night. Common Factor – Inj. Esoz, B.No: 1911039. All the patients were not on OHA. All the patients had increased insulin levels .

Dr. K. Abirami

Dr. K. Abirami

Deputy Medical Administrator

Dr. Bini Susan Isaac

Dr. Bini Susan Isaac

Clinical Pharmacist

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