What are the potential side effects of Linzess (linaclotide)?

Potential Side Effects of Linzess (Linaclotide)

Diarrhea is the most common side effect of Linzess (linaclotide), occurring in 16% of patients with chronic idiopathic constipation and can sometimes be severe, requiring discontinuation of the medication. 1

Common Side Effects

Linzess can cause several gastrointestinal side effects, with varying frequencies:

• Gastrointestinal side effects:

  • Diarrhea (16%) 1
  • Abdominal pain (7%) 1
  • Flatulence (6%) 1
  • Abdominal distension (3%) 1
  • Nausea (reported in post-marketing surveillance) 1

• Other common side effects:

  • Upper respiratory tract infection (5%) 1
  • Sinusitis (3%) 1

Severe Side Effects

While most side effects are mild to moderate, some patients may experience more serious adverse reactions:

• Severe diarrhea: Reported in 2% of patients taking the 145 mcg dose 1
• Treatment discontinuation: Between 5-8% of patients discontinue Linzess due to adverse effects, with diarrhea being the most common reason (3-5%) 2
• Rare but serious side effects:
  • Hematochezia (blood in stool) 1
  • Rectal hemorrhage 1
  • Hypersensitivity reactions including anaphylaxis, angioedema, and rash/urticaria 1

Timing of Side Effects

The majority of diarrhea cases occur within the first 2 weeks of treatment 1. This is important to note as patients should be counseled about this expected timeline.

Special Considerations

• Contraindications: Linzess is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction 2
• Administration: Should be taken on an empty stomach, at least 30 minutes before the first meal of the day 2
• Pediatric concerns: Linzess is contraindicated in children under 6 years of age 1

Management of Side Effects

For patients experiencing diarrhea:

• If severe, discontinue Linzess and contact healthcare provider 1
• Consider dose reduction (from 145 mcg to 72 mcg) if diarrhea is bothersome but not severe 2
• Ensure adequate hydration

Clinical Pearls

• The mechanism of action of linaclotide involves stimulating cyclic guanosine monophosphate (cGMP) production, which increases intestinal fluid secretion and accelerates transit 2
• Linaclotide may also have visceral analgesic activity, which can help with abdominal pain in IBS-C patients 2
• Diarrhea is a direct consequence of linaclotide's mechanism of action, as it increases intestinal fluid secretion 3
• Despite the side effect profile, linaclotide is considered one of the most efficacious secretagogues available for IBS-C 2

When prescribing Linzess, it's important to provide clear instructions about taking it on an empty stomach and to warn patients about the likelihood of diarrhea, particularly in the first two weeks of treatment. Patients should be advised to contact their healthcare provider if they experience severe diarrhea or other concerning symptoms.