D: Use in LIFE-THREATENING emergencies when no safer drug available. Animal studies show risk and human studies not available or neither animal nor human studies done. C: Use with caution if benefits outweigh risks. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

Controlled studies in pregnant women show no evidence of fetal risk. Unknown whether negligible systemic absorption of linaclotide by adults will result in a clinically relevant exposure to breastfed infants Pregnancy CategoriesДЄ: Generally acceptable. No lactation studies in animals have been conducted Maternal use of the drug is not expected to result in exposure to the drug or its active metabolite in breastfed infants there is no information on effects on milk production consider developmental and health benefits of breastfeeding along with the motherвЂ™s clinical need for therapy and any potential adverse effects on breastfed infant from the drug or from the underlying maternal condition Linaclotide and its active metabolite were not detected in the milk of lactating women in adults, concentrations of linaclotide and its active metabolite were below the limit of quantitation in plasma following multiple doses of the drug

Severe maternal toxicity associated with effects on fetal morphology were observed in mice.

No effects on embryofetal development were observed with oral administration of linaclotide in rats and rabbits during organogenesis at doses much higher than the maximum recommended human dosage.

Insufficient data available data on use in pregnant women to inform any drug-associated risk for major birth defects and miscarriage Animal data Linaclotide and its active metabolite are negligibly absorbed systemically following oral administration, and maternal use is not expected to result in fetal exposure

If severe diarrhea occurs, suspend dosing and rehydrate.In postmarketing reports, severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or IV fluid administration have been reported.Diarrhea was the most common adverse reaction in clinical trials.Safety and efficacy in patients aged There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to In neonatal mice, fluid secretion increased because of GC-C agonism resulting in mortality within the first 24 hr due to dehydration.Contraindicated in patients Known or suspected mechanical gastrointestinal obstruction Cautions Pediatric risk Patients aged <2 years due to risk of serious dehydration In nonclinical studies in neonatal mice, oral administration of a single, clinically relevant adult dose of linaclotide caused deaths due to dehydration Contraindications Risk of serious dehydration in pediatric patientsД¬ontraindicated in pediatric patients aged <2 years

Linzess 290 mcg