Products
Linaclotide is commercially available in capsule form (Constella). It was first approved in the United States in 2012 and was reregistered in many countries in 2013.
Structure and properties
Linaclotide (C59H79N15O21S6, Mr = 1526.8 g/mol) is a peptide consisting of 14 amino acids. It has the following sequence. The cysteines are linked to each other by disulfide bridges: H-Cys-Cys-Glu-Tyr-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys-Tyr-OH Linaclotide exists as an amorphous white powder that is sparingly soluble in water. The development of the compound is based on the discovery of bacterial enterotoxins from , which cause diarrhea.
Effects
Linaclotide (ATC A06AX04) has digestive and local analgesic properties. The effects are due to binding to guanylate cyclase-C on intestinal epithelial cells. Linaclotide acts locally in the intestine and increases the concentration of cGMP (cyclic guanosine monophosphate). This activates the CFTR ion channel, leading to an increase in the secretion of chloride, bicarbonate, and water into the lumen of the digestive tract.
Indications
- Irritable bowel syndrome with constipation (IBS-C).
- Chronic idiopathic constipation
Dosage
According to the professional information. The capsules are taken once a day fasting at least half an hour before the first meal. Different dosages are available for different clinical pictures.
Contraindications
- Hypersensitivity
- Children up to 6 years
- Known or suspected gastrointestinal obstruction.
Refer to the drug label for complete precautions.
Interactions
No drug-drug interactions have been reported to date. The risk for systemic interactions is considered low because linaclotide acts locally in the intestine and is barely measurable in plasma after ingestion.
Adverse effects
The most common potential adverse effects include diarrhea, abdominal pain, flatulence, and a bloated abdomen. Treatment should be discontinued if severe diarrhea occurs.
