What are the potential side effects of Losec (omeprazole) in patients, particularly older adults or those with a history of gastrointestinal issues?

Side Effects of Losec (Omeprazole)

Most Common Side Effects

The most frequently reported side effects of omeprazole include headache, stomach pain, nausea, diarrhea, vomiting, and gas, which occur in routine clinical use and are generally mild and self-limiting. 1

• In pediatric patients aged 2-16 years, respiratory system events and fever are additionally common 1
• Gastrointestinal complaints (nausea and diarrhea) represent the most commonly reported adverse effects in clinical practice 2

Serious Adverse Effects Requiring Immediate Medical Attention

Acute Kidney Injury

• Acute tubulointerstitial nephritis (TIN) can occur at any point during PPI therapy, presenting with varying signs from symptomatic hypersensitivity reactions to non-specific symptoms like malaise, nausea, or anorexia 1
• Patients may be diagnosed on biopsy even without extra-renal manifestations such as fever, rash, or arthralgia 1
• Among reported cases, AIN was diagnosed after an average of 2.7 months of therapy with 20-40 mg omeprazole daily, with recurrence universal on rechallenge 3
• Typical laboratory features include hematuria, proteinuria, pyuria, eosinophilia, and anemia 3

Clostridium difficile-Associated Diarrhea

• PPI therapy is associated with increased risk of C. difficile-associated diarrhea, especially in hospitalized patients 1
• This diagnosis should be considered for diarrhea that does not improve during treatment 1

Bone Fractures

• Long-term PPI therapy (≥1 year) and high-dose therapy (multiple daily doses) are associated with increased risk of osteoporosis-related fractures of the hip, wrist, or spine 1
• Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines 1

Vitamin and Mineral Deficiencies

• Vitamin B-12 deficiency can develop with long-term use (>3 years) because stomach acid is needed to absorb vitamin B-12 properly 1
• Low magnesium levels can occur in patients taking PPIs for at least 3 months, usually after a year of treatment 1
• Symptoms of low magnesium include seizures, jitteriness, spasms of hands and feet, dizziness, jerking movements or tremors, cramps or muscle aches, abnormal or fast heartbeat, muscle weakness, and spasm of the voice box 1
• Magnesium levels should be checked before starting long-term therapy and periodically during treatment 1

Lupus Erythematosus

• Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including omeprazole 1
• The most common form is subacute cutaneous lupus erythematosus (SCLE), occurring within weeks to years after continuous therapy 1
• PPI-associated SLE is usually milder than non-drug-induced SLE, with onset typically within days to years after initiating treatment 1
• The majority of patients present with rash, though arthralgia and cytopenia are also reported 1

Fundic Gland Polyps

• Long-term PPI use (>1 year) increases risk of developing fundic gland polyps, a type of stomach growth 1

Severe Allergic Reactions

• Serious hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, and urticaria have been reported 1
• Symptoms requiring immediate medical attention include rash, throat tightness, face swelling, and difficulty breathing 1

Cardiovascular and Hematologic Effects

• Cardiovascular adverse effects include chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, and peripheral edema 1
• Hematologic effects include agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, and leukopenia 1

Hepatic Effects

• The most frequently reported laboratory abnormality is elevation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations 2
• Hepatic adverse effects include elevated liver enzymes (ALT, AST, GGT, alkaline phosphatase, and bilirubin) 1

Dermatologic Reactions

• Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus, and erythema multiforme have been reported 1
• Cutaneous leucocytoclastic vasculitis has been reported in association with omeprazole 4
• Other skin reactions include photosensitivity, urticaria, rash, skin inflammation, pruritus, petechiae, purpura, alopecia, dry skin, and hyperhidrosis 1

Gastrointestinal Effects Beyond Common Side Effects

• Serious gastrointestinal effects include pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, and microscopic colitis 1
• Omeprazole may exacerbate or induce small intestinal mucosal injury in some patients, as demonstrated in case reports where small intestinal mucosal breaks increased or newly appeared after 2 weeks of omeprazole 20 mg daily 5

Neurologic and Sensory Effects

• Neurologic effects include dizziness (2% in clinical trials) 1
• Ophthalmic effects include optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, and double vision 1
• Sensory effects include tinnitus and taste perversion 1

Other Adverse Effects

• Endocrine effects include gynecomastia 1
• Urogenital effects include interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, and testicular pain 1
• General effects include hypersensitivity reactions, fever, pain, fatigue, and malaise 1

Critical Pitfalls and Monitoring Recommendations

• Do not ignore symptoms of acute kidney injury (malaise, nausea, anorexia) as they may represent acute tubulointerstitial nephritis even without classic hypersensitivity symptoms 1, 3
• Check magnesium levels before starting long-term therapy and periodically during treatment, especially if therapy will exceed 3 months 1
• Consider vitamin B-12 deficiency screening in patients on omeprazole for more than 3 years 1
• Use the lowest effective dose and shortest duration appropriate to the condition being treated to minimize risks of bone fractures, C. difficile infection, and other long-term complications 1
• Avoid administration of PPIs for longer than medically indicated, particularly given the risk of cutaneous and systemic lupus erythematosus 1
• Discontinue omeprazole immediately if severe allergic reactions, severe skin reactions, or suspected acute tubulointerstitial nephritis occur 1