Drug Interaction:
No drug-drug interaction studies have been conducted with LINZESS.
Linaclotide and its active metabolite are not measurable in plasma
following administration of the recommended clinical doses; hence,
no systemic drug-drug interactions or drug interactions mediated
by plasma protein binding of linaclotide or its metabolite are anticipated
Linaclotide does not interact with the cytochrome P450 enzyme system based
on the results of in vitro studies. In addition, linaclotide is neither a substrate
nor an inhibitor of the efflux transporter Pglycoprotein (P-gp).
Indication:
LINZESS (linaclotide) capsules, for oral use
Initial U.S. Approval: 2012
WARNING: PEDIATRIC RISK
See full prescribing information for complete boxed warning.
LINZESS is contraindicated in pediatric patients up to 6 years of age; linaclotide
caused deaths due todehydration in young juvenile mice.
Avoid use of LINZESS in pediatric patients 6 through 17 years of age.
The safety and efficacy of LINZESS has not been established in pediatric patients under
18 years of age
RECENT MAJOR CHANGES
Boxed Warning 7/2014
Contraindications 7/2014
Warnings and Precautions,
Pediatric Risk 7/2014
Warnings and Precautions, Diarrhea 7/2014
Drug Name- Linzess
Active Ingredient - Linaclotide
To treat chronic idiopathic constipation and to treat irritable bowel syndrome
with constipation (IBS-C) in adults
Indication-
To treat chronic idiopathic constipation and to treat irritable bowel syndrome
with constipation (IBS-C) in adults
Approved by FDA on 30-8--2012 (Ref- FDA Approved List- 2012)
Adverse Reaction:
Most common adverse reactions (incidence of at least 2%) reported in IBS-C
or CIC patients are diarrhea, abdominal pain, flatulence and abdominal distension.
Contra-Indications:
LINZESS is contraindicated in pediatric patients up to 6 years of age; linaclotide
caused deaths due todehydration in young juvenile mice.
Avoid use of LINZESS in pediatric patients 6 through 17 years of age.
The safety and efficacy of LINZESS has not been established in pediatric patients under
18 years of age
Patients with known or suspected mechanical gastrointestinal obstruction
WARNINGS AND PRECAUTIONS
Diarrhea: Patients may experience severe diarrhea. Hold or stop LINZESS
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
LINZESS
is a guanylate cyclase-C agonist indicated in adults for treatment of:
Irritable bowel syndrome with constipation (IBS-C)
Chronic idiopathic constipation (CIC)
DOSAGE AND ADMINISTRATION
IBS-C: Take 290 mcg orally once daily
CIC: Take 145 mcg orally once daily
Take on empty stomach at least 30 minutes prior to first meal of the day
DOSAGE FORMS AND STRENGTHS
Capsules: 145 mcg and 290 mcg
Patient Information:
PATIENT COUNSELING INFORMATION
Patients should be instructed as follows:
1.Do not give LINZESS to children who are under 6 years of age. It may harm them.
You should not give LINZESS to children 6 to 17 years of age.
It may harm them
2.Keep LINZESS in the original container. Do not subdivide or repackage.
Protect from moisture. Do not remove desiccant from the container.
Keep bottles closed tightly in a dry place
3.Take LINZESS once daily on an empty stomach as prescribed.
Swallow the capsule whole and do not break apart or chew
4.If you miss a dose, skip the missed dose. Just take the next dose
at your regular time. Do not take 2 doses at the same time.
5.Stop LINZESS and contact your physician if you experience severe diarrhea .
Seek immediate medical attention if you develop unusual or severe abdominal pain, and /or severe diarrhea, especially if in combination with hematochezia or melena
Pharmacology/ Pharmacokinetics:
1. Mechanism of Action
Linaclotide is a guanylate cyclase-C (GC-C) agonist. Both linaclotide and its
active metabolite bind to GCC and act locally on the luminal surface of the
intestinal epithelium. Activation of GC-C results in an increase in both
intracellular and extracellular concentrations of cyclic guanosine
monophosphate (cGMP).
2. Pharmacokinetics
Absorption LINZESS is minimally absorbed with low systemic availability following
oral administration. Concentrations of linaclotide and its active metabolite
in plasma are below the limit of quantitation after oral doses of 145 mcg
or 290 mcg were administered.
Therefore, standard pharmacokinetic parameters such as area under the
curve (AUC), maximum concentration (Cmax), and half-life (t½) cannot
be calculated
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category C
Risk Summary There are no adequate and well-controlled studies with LINZESS
in pregnant women. In animal developmental studies, adverse fetal effects
were observed only with maternal toxicity and at doses of linaclotide much
higher than the maximum recommended human dose.
LINZESS should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
2. Nursing Mothers
It is not known whether linaclotide is excreted in human milk; however, linaclotide
and its active metabolite are not measurable in plasma following administration
of the recommended clinical doses
Caution should be exercised when LINZESS is administered to nursing women
3. Pediatric Use
LINZESS is contraindicated in children under 6 years of age. The safety and
effectiveness of LINZESS in pediatric patients under 18 years of age have
not been established.
Avoid use of LINZESS in pediatric patients 6 through 17 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 LINZESS in pediatric patients
6 through 17 years of age
4. Geriatric Use
Irritable Bowel Syndrome with Constipation (IBS-C) Of 1605 IBS-C patients
in the placebo-controlled clinical studies of LINZESS, 85 (5%) were at
least 65 years of age, while 20 (1%) were at least 75 years old.
Clinical studies of LINZESS did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from
younger subjects.
Manufacturer Details