Proton Pump Inhibitors – Emerging Litigation

Proton-pump inhibitors (PPIs) are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production.  They are the most potent inhibitors of acid secretion available.  This group of drugs followed and largely superseded another group of medications with similar effects, but a different mode of action, called H2-receptor antagonists.

Manufacturer:  Omeprazole was first marketed in the United States in 1989 by Astra AB, now AstraZeneca, under the brand name Losec.  In 1990, at the request of the U.S. Food and Drug Administration, the brand name Losec was changed to Prilosec to avoid confusion with the diuretic Lasix (furosemide).

When Prilosec’s U.S. patent expired in April 2001, AstraZeneca introduced esomeprazole (Nexium) as a patented replacement drug.  Many companies introduced generics as AstraZeneca’s patents expired worldwide, which are available under many brand names.

Mechanism of Action:

Proton-pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system of the gastric parietal cells.  The proton-pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.

Targeting the terminal step in acid production, as well as the irreversible nature of the inhibition, results in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%.

Decreasing the acid in the stomach can aid the healing of duodenal ulcers and reduce the pain from indigestion and heartburn.  Stomach acids are needed however to digest proteins, vitamin B12, calcium, and other nutrients.  Too little stomach acid causes the condition hypochlorhydria.

The PPIs are given in an inactive form, which is neutrally charged and readily crosses cell membranes into intracellular compartments (like the parietal cell canaliculus) with acidic environments.  In an acid environment, the inactive drug is protonated and rearranges into its active form.  As described above, the active form will covalently and irreversibly bind to the gastric proton pump, deactivating it.

Proton Pump Inhibitor (PPI) Side Effects

·         Acute interstitial nephritis (inflammation of the kidneys).

·         Acute kidney injury.

·         Chronic kidney disease (CKD).

·         Kidney failure (renal failure).

·         Cardiac disorders

·         Heart attack

·         Stroke

·         Bone fractures (hip fracture, wrist fracture, spine fracture)

·         Broken bones

·         Low magnesium levels (hypomagnesemia)

·         Gut infections

·         Dementia

·         Erectile dysfunction (ED)

·         Severe allergic reactions

·         And more

CASE REVIEW FOCUS AREAS:

1. PPI Intake Details – Dose, Duration (Prilosec/Nexium)?

2. Reason necessitating PPI Intake (Prilosec/Nexium)?

3. Frequency and treatment details (Prilosec/Nexium)

Critical Review of Pharmacy Records and Bills for prescription/OTC

Physician Recommendation

  • Did the plaintiff have any pre-existing conditions or contraindications predisposing to chronic kidney disease?
  • The plaintiff’s CKD stage from the last available records (refer to CKD Stages)
  • When and where was the injury diagnosed?
  • Diagnostics performed – Laboratories (blood and urinalysis measuring calcium, magnesium, and other nutrient levels), invasive and non-invasive diagnostics procedures – GFR, ultrasound, MRI, CT, PET, biopsy, etc.
  • Treatment/management. Any complications
  • Follow-up visits for treatment/management of complications.
  • Outcome/prognosis. Resolution of complications?

Specific Focus:

Identify and report cases with the following scenarios: –

  1. No Injuries: Plaintiff had treatment but did not develop any injuries
  2. Any medical/surgical/Family history, social history that could have had an effect

Proton Pump Inhibitor Warnings

The February 2016 issue of JAMA, the Journal of the American Medical Association, published results of a study which indicated that long-term use of PPI medications may increase the risk of the development of chronic kidney disease (CKD).  The study indicated that the 10-year risk of CKD in PPI users was 20 to 50 percent higher than those who had not taken the medications.  The study also showed that the longer a person takes the medications, the greater the risk and patients who took the medications more than once a day were more likely to develop the condition.

In addition to the recently confirmed risk of kidney failure, in June of 2015, the medical journal, PLOS One, reported the results of two studies which showed that PPI use may cause an increased risk of heart attack by as much as 21 percent.

PPI use has been linked to other serious side effects in the past including a 2006 study which showed an increased risk of bone-fractures in the elderly.  This study eventually resulted in a 2010 warning issued by the Food and Drug Administration regarding bone fracture risk.  In 2009, a study conducted in Copenhagen reported that PPI use may produce a “rebound” acid effect, likening the condition to “dependency” on the medications.

In 2010, investigations were completed regarding a reported increase in risk of cardiac birth defects when PPIs were used during pregnancy.  The FDA concluded that there was not a statistically significant link but one PPI (omeprazole or Prilosec) is listed as Pregnancy Category C, indicating that animal studies have shown a potential risk to developing fetuses.  Birth defects have been cited as a claim in multiple PPI lawsuits, though no settlements have been reached.

In 2011, a notice was issued by the FDA about PPI-induced hypomagnesemia after long term use of the medications.  Low magnesium levels can result in neurological and muscular effects including seizure and effects on the heart.  Observational studies have also shown a possible link to other PPI-related serious adverse events including interstitial nephritis, acquired infections and other conditions, but more study is needed for confirmation.

No action has been taken yet about the reported link between PPI use and chronic kidney disease, kidney failure or heart attacks by the FDA or PPI manufacturers.

Birth defects, bone fractures, and other serious events have been cited as a claim in multiple PPI lawsuits, though no settlements have been reached.

 

Missing record communication:

Identify and report on missing medical records

Apart from identifying critical missing records that are important for the case, provide a detailed outline on what records are needed, why we need them, how did we get a clue that these records are missing and whether the records missing are confirmatory/probable. This will also help in following up and retrieving the records.

Missing Records are presented in the following format

 

What Records/Medical Bills are NeededHospital/

Medical Provider

Date/Time PeriodWhy we need the Records/BillsIs Record Missing Confirmatory or Probable?Hint/Clue that records are missing


CKD stages

StageGFRDescriptionAssessmentTreatment Stage
190+Normal kidney function, but urine findings or structural abnormalities or genetic trait point to kidney disease·     Proteinuria or hematuria

·     Genetic diagnosis of kidney disease

·     Evidence of structurally abnormal kidney

Observation, control or blood pressure.
260-89Mildly reduced kidney function, and other findings (as for stage 1) point to kidney disease.·      Proteinuria or hematuria

·      Genetic diagnosis of kidney disease

·      Evidence of structurally abnormal kidney

Observation, control of blood pressure and risk factors.
3A

3B

45-59

30-44

Moderately reduced kidney function.·      Clinical Assessment:  for sepsis, heart failure, hypovolemia, bladder enlargement.

·      Urine tests:  Dipstick for blood and quantitation of proteinuria.

·      Imaging

Observation, control of blood pressure and risk factors.
415-29Severely reduced kidney function·      Clinical Assessment:  for sepsis, heart failure, hypovolemia, bladder enlargement, cardiovascular system.

·      Urine tests:  Dipstick for blood and quantitation of proteinuria.

·      Blood tests:  Calcium, phosphate, and Hb

·      Imaging

Planning for endstage renal failure.
5<15 or on dialysisVery severe, or endstage kidney failure (sometimes call established renal failure)·      Clinical Assessment:  for sepsis, heart failure, hypovolemia, bladder enlargement, cardiovascular system.

·      Urine tests:  Dipstick for blood and quantitation of proteinuria.

·      Blood tests:  Calcium, phosphate, and Hb

·      Imaging

Treatment choices.