Constella (Linaclotide)

What Is Constella and What Is It Used For?

Quick Answer: Constella contains linaclotide, a guanylate cyclase-C agonist that treats moderate to severe irritable bowel syndrome with constipation (IBS-C) in adults. It relieves abdominal pain, bloating, and constipation by acting directly in the intestine.

Constella is a prescription medicine specifically developed for the treatment of irritable bowel syndrome with constipation (IBS-C). IBS is one of the most common functional gastrointestinal disorders worldwide, affecting an estimated 10 to 15 percent of the global population, with a significant proportion experiencing the constipation-predominant subtype. The condition is characterized by chronic or recurrent abdominal pain associated with altered bowel habits, and it can substantially impair quality of life, work productivity, and psychological wellbeing.

The active ingredient in Constella is linaclotide, a synthetic 14-amino-acid peptide that acts as a guanylate cyclase-C (GC-C) agonist. Unlike many other gastrointestinal medications, linaclotide works locally within the intestinal lumen and is minimally absorbed into the bloodstream. This targeted mechanism of action means that it exerts its therapeutic effects directly where they are needed while minimizing the potential for systemic side effects.

The main symptoms of IBS with constipation that Constella is designed to address include:

• Abdominal pain and discomfort – often described as cramping, aching, or sharp pains in the lower abdomen
• Bloating and abdominal distension – a sensation of fullness or swelling in the abdomen
• Constipation – characterized by infrequent bowel movements, hard or pellet-like stools, and straining during defecation
• Incomplete evacuation – the feeling that the bowel has not been fully emptied

How Constella Works

Constella works through a dual mechanism of action that addresses both the pain and the motility components of IBS-C. When taken orally, linaclotide binds to guanylate cyclase-C (GC-C) receptors located on the luminal surface of intestinal epithelial cells. This binding triggers a cascade of intracellular events that lead to increased concentrations of cyclic guanosine monophosphate (cGMP) both inside and outside the cells.

The increase in intracellular cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, which promotes the secretion of chloride and bicarbonate ions into the intestinal lumen. This draws water into the gut, softening stool consistency, increasing stool volume, and accelerating gastrointestinal transit. The net effect is an improvement in constipation symptoms, including more frequent and easier bowel movements.

Simultaneously, the extracellular cGMP that accumulates in the submucosal space acts on pain-sensing nerve fibers (nociceptors), reducing their firing threshold and decreasing visceral hypersensitivity. This mechanism is responsible for the analgesic effect of Constella, reducing the abdominal pain that is a hallmark of IBS-C. Clinical trials have demonstrated that this dual mechanism provides meaningful relief of both constipation and pain symptoms in the majority of patients.

Constella was approved by the European Medicines Agency (EMA) in 2012 and is marketed in Europe by AbbVie. In the United States, the same active substance is available under the brand name Linzess (manufactured by AbbVie/Allergan). The drug has been extensively studied in large, randomized, placebo-controlled clinical trials involving thousands of patients, establishing its efficacy and safety profile for the treatment of IBS-C.

What Should You Know Before Taking Constella?

Quick Answer: Do not take Constella if you are allergic to linaclotide or have a known bowel obstruction. Inform your doctor about any history of inflammatory bowel disease, cardiovascular conditions, or if you are taking medications whose absorption may be affected by diarrhea.

Contraindications

There are specific situations in which Constella must not be used. Understanding these contraindications is essential for safe treatment. You should not take Constella if:

• You are allergic to linaclotide or any of the other ingredients in the capsule (including microcrystalline cellulose, hypromellose, calcium chloride dihydrate, leucine, gelatin, titanium dioxide, iron oxides, and polyethylene glycol)
• You have, or your doctor suspects you have, a mechanical blockage (obstruction) in your stomach or intestines. This includes conditions such as bowel strictures, adhesions, or tumors that physically block the passage of intestinal contents

Your doctor will have prescribed Constella only after ruling out other conditions that may mimic the symptoms of IBS-C, such as colorectal cancer, inflammatory bowel disease, celiac disease, and thyroid disorders. It is important that you report any changes in your symptoms or new symptoms to your doctor promptly, as these could indicate a different underlying condition.

Warnings and Precautions

Several important warnings and precautions should be considered before and during treatment with Constella:

Special caution is advised in the following situations:

• Age over 65: Elderly patients have a higher risk of developing diarrhea during treatment with Constella. Careful monitoring and adequate hydration are particularly important in this age group.
• Severe or prolonged diarrhea with coexisting conditions: If you have high blood pressure, a history of heart disease (such as previous heart attack), or diabetes, diarrhea-related dehydration and electrolyte imbalances may pose additional health risks.
• Gastrointestinal bleeding: Tell your doctor if you experience any bleeding from the gastrointestinal tract or rectum.
• Inflammatory bowel disease: Constella is not recommended for patients with Crohn's disease or ulcerative colitis, as its safety and efficacy have not been established in these populations.

Children and Adolescents

Constella must not be given to children and adolescents under 18 years of age. The safety and efficacy of linaclotide have not been established in this age group. Pediatric use is specifically contraindicated because young children may be at increased risk of serious dehydration from the diarrhea that this medication commonly causes. Animal studies have shown severe dehydration and death in neonatal mice given linaclotide, underscoring the importance of keeping this medication out of reach of children.

Pregnancy and Breastfeeding

There is limited clinical data on the use of Constella in pregnant women. Because linaclotide acts locally in the gut and is minimally absorbed systemically, the theoretical risk to a developing fetus is considered low. However, as a precautionary measure, Constella should only be used during pregnancy if the potential benefit justifies the potential risk, and only after consulting with your doctor.

Regarding breastfeeding, a dedicated study in seven lactating women who were already being treated with linaclotide found that neither linaclotide nor its active metabolite were detectable in breast milk. This finding is consistent with the drug's minimal systemic absorption. Based on this evidence, Constella can be used during breastfeeding, as nursing infants are not expected to be exposed to the medication through breast milk.

Driving and Operating Machinery

Constella is not expected to affect your ability to drive or operate machinery. No studies specifically examining the effect of linaclotide on driving performance have been conducted. However, dizziness is listed as a common side effect, so patients who experience dizziness should exercise caution when driving or using machinery.

How Does Constella Interact with Other Drugs?

Quick Answer: Constella itself has no known direct drug-drug interactions based on its local mechanism of action. However, the diarrhea it commonly causes can impair the absorption of other oral medications, particularly oral contraceptives, levothyroxine, and drugs requiring precise dosing.

Because linaclotide acts locally in the intestine and is minimally absorbed into the bloodstream, it does not undergo hepatic metabolism and does not interact with cytochrome P450 enzymes. This means there are no classical pharmacokinetic drug-drug interactions with Constella. However, the most clinically relevant interaction concern relates to the diarrhea that Constella can cause, which may affect the absorption and efficacy of concurrently administered oral medications.

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take. The following interactions are particularly important:

Medications Affected by Diarrhea

Severe or prolonged diarrhea caused by Constella can reduce the absorption and effectiveness of certain oral medications. This is especially relevant for drugs with a narrow therapeutic index or those requiring consistent blood levels:

Medications That May Increase the Risk of Diarrhea

Certain medications may have an additive effect on diarrhea when taken together with Constella. While these combinations are not strictly contraindicated, additional caution is warranted:

Food Interactions

Constella should be taken at least 30 minutes before a meal on an empty stomach. Clinical studies have shown that taking Constella with food increases the frequency of bowel movements and the incidence of diarrhea compared to taking it in a fasted state. There are no specific food restrictions beyond this timing recommendation. Patients should maintain a balanced diet and adequate fluid intake throughout treatment.

What Is the Correct Dosage of Constella?

Quick Answer: The recommended dose is one Constella 290 microgram capsule taken by mouth once daily, at least 30 minutes before a meal. Swallow the capsule whole – do not crush, chew, or open it.

Always take Constella exactly as your doctor has told you. If you are unsure, check with your doctor or pharmacist. The dosing regimen for Constella is straightforward, but correct timing and method of administration are important for optimal efficacy and tolerability.

Adults

Taking the capsule on an empty stomach is important because food increases the likelihood and severity of diarrhea. The recommended timing of at least 30 minutes before eating provides the drug with the opportunity to exert its local effects in the intestine before the digestive process begins. Many patients find it convenient to take their capsule first thing in the morning upon waking, and then have breakfast at least 30 minutes later.

If you do not experience any improvement in your symptoms after 4 weeks of treatment, you should contact your doctor. They may reassess your diagnosis or consider alternative treatment approaches. In clinical trials, meaningful improvement in both abdominal pain and constipation symptoms was typically observed within the first 1 to 4 weeks of treatment.

Children and Adolescents

Elderly Patients

No dose adjustment is necessary for elderly patients. However, because patients over 65 years of age are at increased risk for diarrhea and its complications (dehydration, electrolyte imbalances, falls associated with dizziness), healthcare providers should counsel elderly patients about the importance of maintaining adequate hydration and recognizing early signs of dehydration.

Renal and Hepatic Impairment

Because linaclotide acts locally in the gastrointestinal tract and is minimally absorbed into systemic circulation, no dose adjustment is necessary for patients with renal (kidney) or hepatic (liver) impairment. The drug is broken down within the intestinal lumen into its active metabolite and further degraded into smaller peptide fragments before being eliminated in the feces.

Missed Dose

If you forget to take a dose of Constella, do not take a double dose to make up for it. Simply skip the missed dose and take your next capsule at the usual time the following day. Consistent daily dosing is recommended for optimal results, but missing a single dose is unlikely to significantly affect your treatment outcome.

Overdose

If you take more Constella than prescribed, the most likely effect is diarrhea. In the event of an overdose, contact your doctor or pharmacist for advice. Supportive care with fluid and electrolyte replacement should be provided if severe diarrhea develops. There is no specific antidote for linaclotide overdose; however, because the drug acts locally and is not significantly absorbed, systemic toxicity is not expected.

Stopping Treatment

Treatment with Constella can be stopped safely at any time. There is no need for gradual dose tapering. However, it is advisable to discuss stopping treatment with your doctor first, especially if you have been taking the medication for an extended period. Your IBS-C symptoms may return after discontinuation, as the drug does not modify the underlying disease process but rather manages its symptoms. If symptoms recur, your doctor may recommend resuming treatment or considering alternative therapies.

What Are the Side Effects of Constella?

Quick Answer: The most common side effect of Constella is diarrhea, affecting more than 1 in 10 people. It is usually short-lived. Other common side effects include abdominal pain, bloating, flatulence, and dizziness. Rare but serious side effects include gastrointestinal perforation.

Like all medicines, Constella can cause side effects, although not everybody gets them. The side effects are categorized below by their frequency of occurrence, based on clinical trial data and post-marketing surveillance. Most side effects are gastrointestinal in nature, reflecting the drug's local mechanism of action in the intestine.

Managing Diarrhea

Since diarrhea is the most common side effect, understanding how to manage it is important for successful treatment. In most cases, diarrhea occurs within the first few weeks of starting Constella and tends to diminish over time as the body adjusts to the medication. The following strategies can help:

• Stay well hydrated – drink plenty of water and consider oral rehydration solutions if diarrhea is more than mild
• Take Constella on an empty stomach – at least 30 minutes before eating, as taking it with food worsens diarrhea
• Monitor for dehydration signs – reduced urine output, dark urine, dry mouth, dizziness, or feeling faint
• Contact your doctor – if diarrhea is severe (watery, frequent), lasts 7 or more days, or is accompanied by blood, fever, or severe cramping

When to Seek Immediate Medical Attention

While most side effects of Constella are manageable, certain symptoms require urgent medical evaluation:

• Severe, persistent abdominal pain that worsens over time (may indicate gastrointestinal perforation)
• Blood in the stool or rectal bleeding
• Signs of severe dehydration: minimal urine output, extreme thirst, rapid heartbeat, confusion, or fainting
• Signs of severe allergic reaction: widespread hives, difficulty breathing, or swelling of the face, lips, or throat

How Should You Store Constella?

Quick Answer: Store Constella below 30°C in its original bottle with the lid tightly closed. Once opened, use the capsules within 18 weeks. Keep out of reach of children and do not swallow the desiccant packets.

Proper storage of Constella is essential to maintain the stability and effectiveness of the capsules. Linaclotide is a peptide-based molecule that can be affected by moisture and heat, which is why specific storage conditions must be followed.

• Temperature: Store at no more than 30°C (86°F). Do not freeze.
• Container: Keep the capsules in the original high-density polyethylene (HDPE) bottle with the lid tightly closed. The bottle has a child-resistant cap and a tamper-evident seal.
• Moisture protection: The bottle contains one or more silica gel desiccant packets to keep the capsules dry. Keep these packets inside the bottle at all times. Do not swallow the desiccant packets.
• Shelf life after opening: Once the bottle is opened, use the capsules within 18 weeks. After this period, discard any remaining capsules.
• Expiry date: Do not use Constella after the expiry date printed on the bottle and carton (after "EXP"). The expiry date refers to the last day of the stated month.
• Visual inspection: Do not use the capsules if you notice any damage to the bottle or any change in the appearance of the capsules.
• Keep out of reach of children: Store the medicine where children cannot see or reach it.

When disposing of unused or expired Constella capsules, do not throw them in household waste or flush them down the toilet. Return them to your pharmacist for safe disposal. This helps protect the environment.

What Does Constella Contain?

Quick Answer: Each Constella capsule contains 290 micrograms of linaclotide as the active ingredient, along with inactive excipients including microcrystalline cellulose, hypromellose, calcium chloride dihydrate, and leucine.

Understanding the composition of your medicine can be important, particularly if you have known allergies to certain excipients or additives. Each Constella hard capsule contains the following:

Active Ingredient

Linaclotide 290 micrograms – a synthetic 14-amino-acid peptide that acts as a guanylate cyclase-C agonist. Linaclotide is structurally related to the endogenous peptides guanylin and uroguanylin, which naturally regulate intestinal fluid and electrolyte transport.

Inactive Ingredients (Excipients)

Capsule contents:

• Microcrystalline cellulose – a common pharmaceutical filler
• Hypromellose (hydroxypropyl methylcellulose) – used as a binder
• Calcium chloride dihydrate – used in the formulation process
• Leucine – an amino acid used as an excipient

Capsule shell:

• Gelatin
• Titanium dioxide (E171)
• Red iron oxide (E172)
• Yellow iron oxide (E172)
• Polyethylene glycol

Capsule printing ink:

• Shellac
• Propylene glycol
• Concentrated ammonia solution
• Potassium hydroxide
• Titanium dioxide (E171)
• Black iron oxide (E172)

Appearance and Packaging

Constella capsules are white to off-white/orange, opaque, hard capsules printed with "290" in grey ink. They are packaged in a white HDPE bottle with a tamper-evident seal and a child-resistant screw cap, along with one or more silica gel desiccant packets. Constella is available in pack sizes of 10, 28, or 90 capsules, as well as multipacks of 112 capsules (4 cartons of 28 capsules each). Not all pack sizes may be marketed in all countries.