Linzela®

0.09% Linaclotide pellets equivalent to Linaclotide INN 72 mcg

Dosage Form: Capsule
Pack Size: 2 X 10's
Composition:

Linzela® 72 capsule: Each capsule contains 0.09% Linaclotide pellets equivalent to Linaclotide INN 72 mcg. 

Linzela® 290 capsule: Each capsule contains 0.09% Linaclotide pellets equivalent to Linaclotide INN 290 mcg.

Description:

Linaclotide is an orally administered, peptide agonist of guanylate cyclase 2C used for the treatment of irritable bowel syndrome. Chemically, it is a heterodetic cyclic peptide and consists of fourteen amino acids. 

Indications:

Linzela® is a guanylate cyclase-C agonist indicated in adults for the treatment of: 

• Chronic idiopathic constipation (CIC) 

• Irritable bowel syndrome with constipation (IBS-C)

Dosage & Administration:

Chronic Idiopathic Constipation (CIC): 6 - 17 years: 72 mcg (1 capsule) once daily. Adult: 72-145 mcg (1-2 capsules) once daily, based on individual presentation or tolerability. 

Irritable Bowel Syndrome with Constipation (IBS-C): Adult: The recommended dosage of Linzela® is 290 mcg orally once daily.

Contraindications:

Linzela® is contraindicated in: 

• Patients less than 6 years of age due to the risk of serious dehydration 

• Patients with known or suspected mechanical gastrointestinal obstruction

Warning & Precautions:

Risk of Serious Dehydration in Pediatric Patients: Linzela® is contraindicated in patients less than 6 years of age. The safety and effectiveness of Linzela® in patients less than 18 years of age have not been established. In neonatal mice (human age equivalent of approximately 0 to 28 days), Linzela® increased fluid secretion as a consequence of GC-C agonism resulting in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, patients less than 6 years of age may be more likely than patients 6 years of age and older to develop severe diarrhea and its potentially serious consequences. 

Avoid use of Linzela® in pediatric patients 6 years to less than 18 years of age. Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, avoid the use of Linzela® in pediatric patients 6 years to less than 18 years of age. 

Diarrhea: It was the most common adverse reaction of Linaclotide-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar between the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg Linaclotide-treated patients, and in <1% of 72 mcg Linaclotide-treated CIC patients.

In post-marketing experience, severe diarrhea associated with dizziness, syncope, hypotension and electrolyte abnormalities (hypokalemia and hyponatremia) requiring hospitalization or intravenous fluid administration have been reported in patients treated with Linaclotide. If severe diarrhea occurs, suspend dosing and rehydrate the patient.

OVERDOSAGE 

Single Linzela® doses of 2897 mcg were administered to 22 healthy subjects; the safety profile in these subjects was consistent with that in the overall Linzela® -treated population, with diarrhea being the most commonly reported adverse reaction. 

DRUG INTERACTIONS

No drug-drug interaction studies have been conducted with Linzela® . Systemic exposures of drug and active metabolite are negligible following oral administration. 

Linzela® does not interact with the cytochrome P450 enzyme system based on the results of in vitro studies. In addition, Linzela® does not interact with common efflux and uptake transporters (including the efflux transporter P-glycoprotein (P-gp)). Based on these in vitro data no drug-drug interactions through modulation of CYP enzymes or common transporters are anticipated. 

Overdose:

Single Linzela® doses of 2897 mcg were administered to 22 healthy subjects; the safety profile in these subjects was consistent with that in the overall Linzela® -treated population, with diarrhea being the most commonly reported adverse reaction. 

Storage Conditions:

Store between 2⁰ - 8⁰ C, frost free & dry place. Keep away from light and out of the reach of children. 

Commercial Pack:

Linzela® 72 capsule: Each box containing 2 x 10’s Capsules in Alu-Alu blister strip. 

Linzela® 290 capsule: Each box containing 1 x 10’s Capsules in Alu-Alu blister strip.