Prilosec Adverse Effects & Lawsuits

Omeprazole (brand name Prilosec) belongs to the widely prescribed class of proton pump inhibitors (PPIs), also known as substituted benzimidazoles^.1 They have the following mechanism of action:²

• PPIs target the stomach's parietal cells, which produce hydrochloric acid (stomach acid).
• Omeprazole irreversibly binds to and inactivates the proton pump enzyme (H+/K+-ATPase) within these cells.
• By inhibiting the pump, omeprazole prevents the secretion of stomach acid, thereby treating acid-related conditions like heartburn, acid reflux (when stomach acid flows back into the esophagus), and ulcers.

Availability of PPIs

Omeprazole is available by prescription and over-the-counter (OTC) under brand names like Prilosec and Losec. Several other PPI medications exist, with varying prescription and OTC options:

• Esomeprazole (Nexium)
• Lansoprazole (Prevacid)
• Rabeprazole (AcipHex) (prescription only)
• Pantoprazole (Protonix) (prescription only)
• Dexlansoprazole (Dexilant) (prescription only)
• Omeprazole with sodium bicarbonate (Zegerid) (OTC)

Market Presence and Rise to Prominence

• PPIs have dominated the acid-related disease treatment landscape since the late 1980s.
• They have largely replaced histamine2 receptor antagonists (H2-blockers, medications that help reduce stomach acid by blocking a certain type of chemical signal in the stomach called histamine) like famotidine (Pepcid AC) and ranitidine (Zantac) due to their superior potency.³

Approved Treatment Applications

PPIs are indicated for a range of conditions, including:⁴

• Treatment of active, benign gastric (stomach) ulcers.
• Relief of symptoms associated with gastroesophageal reflux disease (GERD) (when stomach acid flows back into the esophagus).
• Healing and maintenance of healing of erosive esophagitis caused by GERD (inflammation of the esophagus due to stomach acid).
• Management of certain pathological hypersecretory conditions (excessive stomach acid production).

While all PPIs are similarly effective, long-term use has been linked to various safety concerns.⁵ The FDA, prompted by adverse event reports, issued broad warnings encompassing all available prescription and OTC PPIs.⁶ The strength of evidence and causal relationships for these potential risks vary considerably. Key areas of safety concern are as follows:^3,5,7-13

• Nutrient Absorption: PPIs may alter the absorption of essential vitamins and minerals like B12, iron, calcium, and magnesium.
• Bone Health: Evidence suggests long-term use of PPIs may have metabolic effects on bone density, potentially raising the risk of fractures
• Drug Interactions: PPIs may alter how other drugs are processed by the body, leading to potential interactions.
• Infection Risks: Concerns exist regarding an increased risk of infections like pneumonia, C. difficile (a type of bacteria that can cause infections in the colon), and small bowel bacterial overgrowth.
• Hypersensitivity Reactions: Allergic reactions to PPIs are possible.
• Kidney Issues: Potential links to acute kidney injury and chronic kidney disease are being investigated.
• Digestive Issues: Atrophic gastritis (stomach lining thinning) and gastric/duodenal polyps (abnormal growths in the stomach and first section of the small intestine, respectively, some of which might turn into cancer) are potential concerns.
• Cancer Risk: The possibility of increased risk for gastric (stomach), pancreatic, colorectal, and liver cancers with PPI use is a subject of ongoing debate.

Specific populations require careful consideration when prescribing omeprazole. Liver impairment, pregnancy, kidney function, and age may necessitate dosage adjustments, as follows:²

Hepatic Impairment

The following considerations should be taken into account in patients with liver disease:

• Omeprazole breakdown occurs in the liver.
• Patients with liver problems may experience a doubling of omeprazole's bioavailability (amount of drug absorbed) due to reduced "first-pass effect" (initial liver metabolism).
• Omeprazole’s half-life (drug elimination time) also increases in these patients (3 hours vs. 0.5-1 hour), necessitating a potential dosage reduction.

Renal Impairment

The following considerations should be taken into account in patients with kidney disease:

• No official dosage adjustments are currently recommended for patients with reduced kidney function.
• While bioavailability may increase slightly in such cases, elimination slows down proportionally.
• Further guidance on renal impairment and omeprazole use may be forthcoming.

Pregnancy and Lactation

The following considerations should be taken into account in pregnant and lactating women:

• Omeprazole crosses the placenta (a special organ that grows in a pregnant person's uterus to provide oxygen and nutrients to the developing baby and remove waste products) and is classified as Pregnancy Category C (potential fetal risks exist).
• Alternative PPIs with a Category B classification (no first-trimester risk identified in human studies) may be preferable for pregnant women.
• Limited data suggests that risk for breastfed babies at typical omeprazole doses (20mg/day) is minimal.

Pediatric and Geriatric Use

The following considerations should be taken into account in older patients and children:

• Omeprazole dosage adjustments are made based on a child's weight for ages 1-16.
• The elimination rate of omeprazole decreases in elderly patients, leading to increased bioavailability (76% vs. 58% in younger adults). This may require a dosage reduction.

Thousands of lawsuits allege Prilosec (omeprazole) caused serious kidney injuries, including:¹⁴

• Acute kidney injury - a sudden and often reversible decrease in kidney function, causing a rapid buildup of waste products in the blood
• Chronic kidney disease - long-term damage to the kidneys leading to gradual loss of function over time
• End-stage renal failure - the final stage of chronic kidney disease where kidneys can no longer function well enough to maintain life, requiring dialysis or kidney transplantation for survival
• Interstitial nephritis - inflammation of the tissue between the kidney tubules, leading to impaired kidney function
• Fractures - associated with decreased bone density

The central legal issue is the alleged failure to warn patients about kidney injury risks, including acute interstitial nephritis and renal failure. Plaintiffs claim the drugmakers, AstraZeneca and Procter & Gamble, knew of these risks as early as 2004 but failed to warn consumers.¹⁴ Some Prilosec lawsuits allege that AstraZeneca knew of kidney risks for at least 10 years before warning the public. Lawsuits claim manufacturers:¹⁵

• Produced a defective and unreasonably dangerous drug
• Were negligent in the production process
• Failed to properly test or warn of risks
• Concealed evidence and misrepresented safety

Damages sought in lawsuits against PPI manufacturers have pursued compensation for kidney injuries, including:¹⁴

• Lost wages
• Medical bills
• Pain and suffering

Prilosec and Nexium kidney damage class action lawsuits are still being filed.¹⁶ The status of cases against PPI manufacturers are as follows:¹⁴

• Over 18,600 PPI lawsuits have been filed, with more than 13,000 against Nexium and Prilosec specifically.
• The lawsuits are currently consolidated in a multidistrict litigation (MDL) overseen by a federal judge in New Jersey for centralized discovery.
• As of May 2023, over 12,900 PPI lawsuits remain active within the MDL.

The Medical Letter on Drugs and Therapeutics report on PPI safety was re-published in JAMA in 2017 and concluded that:⁵

• Long-term PPI use has been associated with an increasing number of safety concerns.
• However, "Few of these concerns are supported by a causal relationship or consistent data. For patients with a clear indication for long-term treatment with a PPI, the benefits probably outweigh the risks."