Lotronex

alosetron hydrochloride

Lotronex

Pharmacologic class: Serotonin receptor antagonist

Therapeutic class: Agent for irritable bowel syndrome

Pregnancy risk category B

FDA Box Warning

• Infrequent but serious GI problems have occurred, resulting in hospitalization and, rarely, blood transfusions, surgery, and death.

• Only physicians enrolled in Glaxo-SmithKline's Prescribing Program for Lotronex should prescribe Lotronex.

• Drug is indicated only for women with severe, diarrhea-predominant irritable bowel syndrome who don't respond adequately to conventional therapy. Patient must read and sign agreement before receiving initial prescription.

• Discontinue immediately if patient develops constipation or ischemic colitis symptoms. Don't resume therapy in patients who developed ischemic colitis. Patients with resolved constipation should resume only on advice of physician.

Action

Inhibits activation of nonselective cation channels, resulting in modulation of enteric nervous system

Availability

Tablets: 0.5 mg, 1 mg

Indications and dosages

Women with severe, diarrhea-predominant irritable bowel syndrome (IBS) who have chronic symptoms not caused by anatomic or biochemical abnormalities and who are unresponsive to conventional therapy

Adult women: Initially, 0.5 mg P.O. b.i.d. If after 4 weeks dose is well tolerated but doesn't adequately control IBS, may increase to 1 mg P.O. b.i.d.; therapy should be discontinued in patients not responding to 1 mg P.O. b.i.d. after 4 weeks.

Contraindications

• Concurrent use of fluvoxamine
• Severe hepatic impairment
• Current constipation or history of chronic or severe constipation
• History of complications related to constipation
• History of intestinal obstruction, stricture, toxic megacolon, GI perforation, or adhesion
• History of ischemic colitis, impaired intestinal circulation, thrombophlebitis, or hypercoagulable state
• Current Crohn's disease or ulcerative colitis, active diverticulitis, or history of these disorders
• Inability to understand or comply with patient-physician agreement for drug

Precautions

Use cautiously in:
• hepatic insufficiency
• moderate CYP/A2 inhibitors, such as quinolone antibiotics and cimetidine (avoid use)
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

Before administering, know that drug is approved with the following marketing restrictions: Ensure that patient understands that drug has serious risks, patient reads and signs patient-physician agreement, and patient follows directions in accompanying medication guide.
• Know that anatomical and biochemical abnormalities of GI tract should be ruled out before drug therapy starts.
• Give with or without food.

Don't administer drug if patient is constipated.

Stop therapy immediately if patient develops constipation or signs or symptoms of ischemic colitis.

Adverse reactions

CNS: anxiety, malaise

CV: increased blood pressure, extrasystoles, tachyarrhythmias, arrhythmias

GI: nausea; constipation; GI pain, discomfort, or spasms; abdominal distention; regurgitation or gastroesophageal reflux; hemorrhoids; decreased salivation; dyspepsia; ischemic colitis; GI perforation; small-bowel mesenteric ischemia

GU: urinary frequency

Hematologic: hemorrhage

Respiratory: breathing disorders

Skin: sweating, urticaria

Other: fatigue, cramps, disturbed temperature regulation

Interactions

Drug-drug.CYP450 inducers or inhibitors: altered alosetron clearance

Fluvoxamine: increased alosetron concentration and half-life

Drug-diagnostic tests.Blood glucose, calcium, phosphate: increased or decreased level

Patient monitoring

Monitor patient closely for adverse reactions, especially such GI reactions as constipation and signs or symptoms of ischemic colitis.

Patient teaching

Make sure patient knows about drug's marketing restrictions, which stipulate that she understands drug has serious risks, that she reads and signs patient-physician agreement, and that she follows directions in accompanying medication guide.
• Tell patient to take drug exactly as prescribed, with or without food.

Instruct patient to contact prescriber immediately if she develops constipation or symptoms of insufficient blood flow to bowel (such as new or worsening pain in bowels or bloody bowel movements).
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

alosetron

(a-low-se-tron) ,

Lotronex

(trade name)

Classification

Therapeutic: anti irritable bowel syndrome agents
Pharmacologic: five ht3 antagonists
Pregnancy Category: B

Indications

Treatment of severe diarrhea-predominant irritable bowel syndrome (IBS) in women who have chronic symptoms (≥6 mo), no other GI pathology, and have had no response to conventional therapy.

Action

5-HT3 receptors are non-selective cation channels responsible for regulation of visceral pain, colonic transit, and GI secretions. Alosetron inhibits the activation of these channels.

Therapeutic effects

Increased colonic transit time without affecting orocecal transit time resulting in decreased pain/discomfort and diarrhea associated with IBS.

Pharmacokinetics

Absorption: 50–60% absorbed following oral administration.
Distribution: 65–95 L.
Protein Binding: 82% bound to plasma proteins.
Metabolism and Excretion: Extensively metabolized by the liver; 13% excreted unchanged in urine.
Half-life: 1.5 hr.

Time/action profile (pain/discomfort, diarrhea)

ROUTEONSETPEAKDURATION
POwithin 1–2 wkup to 6 wk1 wk†
†Following discontinuation

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Constipation; History of chronic/severe constipation or complications due to constipation; History of GI obstruction, stricture, toxic megacolon, perforation, and/or adhesions; History of ischemic colitis, ↓ intestinal circulation, thrombophlebitis, or coagulation defects; History of Crohn’s disease/ulcerative colitis/diverticulitis; Severe hepatic impairment; Concurrent use of fluvoxamine; Patients unable to understand or comply with Patient Acknowledgement Form.
Use Cautiously in: Men – safety not established; Mild-moderate hepatic impairment; Patients who are elderly, debilitated, or taking medications that ↓ GI motility; Obstetric / Lactation / Pediatric: Safety not established.

Adverse Reactions/Side Effects

Gastrointestinal

  • acute ischemic colitis (life-threatening)
  • toxic megacolon (life-threatening)
  • constipation (most frequent)
  • abdominal discomfort
  • abdominal distention
  • flatulence
  • nausea
  • GI viral infections
  • hemorrhoids
  • regurgitation or reflux

Interactions

Drug-Drug interaction

Fluvoxamine can ↑ levels; concurrent use contraindicated).Amiodarone, cimetidine, ciprofloxacin, clarithromycin, itraconazole, ketoconazole, ofloxacin, protease inhibitors, telithromycin, and voriconazole may ↑ levels; use concomitantly with caution.

Route/Dosage

Oral (Adults) Women—0.5 mg twice daily.

Availability

Tablets: 0.5 mg, 1 mg

Nursing implications

Nursing assessment

  • Monitor patient for signs of constipation or ischemic colitis (new or worsening abdominal pain, bloody diarrhea, blood in stool) throughout therapy. Patients should not start taking alosetron if they are constipated.
  • Discontinue therapy immediately if patient develops constipation or signs/symptoms of ischemic colitis.

Potential Nursing Diagnoses

Diarrhea (Indications)
Risk for constipation (Side Effects)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Do not confuse Lotronex with Protonix.
  • Alosetron should only be prescribed by physicians enrolled in GlaxoSmithKline’s Prescribing Program for Alosetron.
  • Oral: Administer 0.5 mg twice daily for 4 wk. If constipation occurs after initiation of therapy, discontinue until constipation resolves, then restart at 0.5 mg once daily (if constipation recurs at this dose, discontinue therapy). If IBS symptoms are not controlled after 4 wk, no constipation has occurred and patient tolerates either 0.5 mg once or twice daily, dose may be increased to 1 mg twice daily. If symptoms are not controlled after 4 wk of 1 mg twice, discontinue alosetron.
  • Can be administered with or without food; however, administration with food may decrease absorption by 25%.

Patient/Family Teaching

  • Instruct patient to take alosetron exactly as directed. If a dose is missed, skip the dose and return to regular schedule; do not double doses. Counsel patients about the risks and benefits of alosetron and the impact of IBS symptoms on their life. Patients should read the Medication Guide before starting alosetron and each time they refill their prescription. The Patient-Physician Agreement should be signed, with the original in the patient’s chart and a copy to the patient, prior to initiating therapy.
  • Caution patient to stop taking alosetron and report constipation or signs of ischemic colitis to health care professional immediately. Immediately contact health care professional again if constipation does not resolve after discontinuation of alosetron. Alosetron should be resumed only after constipation has resolved and on the advice of their health care professional. Treatment with alosetron should not be resumed in patients who develop ischemic colitis.

Evaluation/Desired Outcomes

  • Increased colonic transit time without affecting orocecal transit time resulting in decreased pain, discomfort, and diarrhea associated with IBS.

Lotronex

An agent used to manage irritable bowel syndrome pulled from the market 6 months after release as constipation occurred in 25% of Pts, and potentially fatal ischemic colitis. See Irritable bowel syndrome.
References in periodicals archive ?
Late last month Amneal Pharmaceuticals LLC began shipping alosetron hydrochloride tablets, an AB-rated generic equivalent to Lotronex, in 0.
These include the constipation-predominant IBS (IBS-C) therapies, Sucampo/Takeda/Abbott's Amitiza (lubiprostone) and Ironwood/Actavis/Almirall/Astellas' Linzess (linaclotide), and the diarrhea-predominant IBS (IBS-D) therapies, Prometheus' Lotronex (alosetron) and Astellas' Irribow (ramosetron).
For example, in response to protests by sufferers of irritable bowel syndrome, the FDA in 2002 permitted the return to the market of Lotronex, a drug earlier withdrawn because of occasional severe side effects.
Lotronex was withdrawn from the market soon after it was introduced because of safety concerns, but it was subsequently reintroduced and is currently available.
043 billion to resolve civil liability under the False Claims Act related to off-label promotion of Advair, Lamictal and Zofran, and kickbacks paid to health care professionals to promote and prescribe those drugs as well as Imitrex, Lotronex, Flovent and Valtrex.
The civil settlement reached with the Government does not constitute an admission of any liability or wrongdoing in the selling and marketing of Lamictal, Zofran, Imitrex, Lotronex, Flovent, Valtrex, Avandia or Advair products, nor in its nominal pricing practices, the company said.
4) The committee ultimately recommended approving the drug without further testing, and the FDA followed the committee's advice and formally approved Lotronex in February 2000.
Physicians who prescribe Lotronex under the risk management program must sign a form saying that they have read the full prescribing information, know what the drug is used for, and have explained the risks of the drug to the patient.