Rowasa

Uses and Indications

This drug is indicated for the treatment of active mild to moderate distal ulcerative colitis, proctosigmoiditis, or proctitis in adults.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

The recommended dosage of ROWASA (mesalamine) rectal suspension is one rectal instillation of 4 grams once daily, preferably administered at bedtime. The instillation should be retained for approximately eight hours. The duration of treatment may vary from 3 to 6 weeks, depending on the patient's symptoms and sigmoidoscopic findings.

ROWASA is intended for rectal use only. Healthcare professionals should ensure that patients are instructed on the proper technique for administration to maximize the therapeutic effect and minimize discomfort.

Contraindications

Use of ROWASA is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, sulfites, or any other ingredients contained in the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Patients receiving ROWASA should be closely monitored for several critical warnings and precautions to ensure safe use of the medication.

Hypersensitivity Reactions ROWASA contains potassium metabisulfite, which may lead to sulfite-related reactions. Additionally, sulfasalazine-associated reactions, such as myocarditis and pericarditis, can occur. Healthcare professionals must evaluate patients immediately and discontinue ROWASA if a hypersensitivity reaction is suspected.

Renal Impairment It is essential to assess renal function at the beginning of treatment and periodically throughout the course of therapy. The risks and benefits of ROWASA should be carefully evaluated in patients with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates during treatment, ROWASA should be discontinued.

Mesalamine-Induced Acute Intolerance Syndrome Healthcare providers should be vigilant for signs of acute intolerance syndrome, which may present as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. If such symptoms are suspected, treatment with ROWASA should be discontinued.

Hepatic Failure The use of ROWASA in patients with known liver impairment requires careful consideration of the associated risks and benefits.

Severe Cutaneous Adverse Reactions At the first signs or symptoms of severe cutaneous adverse reactions or other indications of hypersensitivity, ROWASA should be discontinued, and further evaluation should be considered.

Photosensitivity Patients should be advised to avoid sun exposure if they have pre-existing skin conditions, as photosensitivity may occur.

Nephrolithiasis Cases of nephrolithiasis have been reported in patients using mesalamine. It is important to note that mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is crucial.

General Precautions Mesalamine may interfere with laboratory tests, specifically leading to elevated urinary normetanephrine test results.

Laboratory Tests Regular assessment of renal function is recommended at the beginning of treatment and periodically thereafter to monitor for any potential complications.

In summary, healthcare professionals should remain vigilant for these warnings and precautions to ensure the safe administration of ROWASA.

Side Effects

Most common adverse reactions occurring in patients treated with ROWASA (≥1%) include gas/flatulence, flu, fever, leg/joint pain, hemorrhoids, rectal pain, and hair loss.

Serious adverse reactions may include hypersensitivity reactions, which can manifest as sulfite-related reactions due to the presence of potassium metabisulfite in ROWASA, as well as sulfasalazine-associated reactions such as myocarditis and pericarditis. Patients should be evaluated immediately, and ROWASA should be discontinued if a hypersensitivity reaction is suspected.

Additionally, mesalamine-induced acute intolerance syndrome may occur, characterized by symptoms such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. Treatment should be discontinued if this syndrome is suspected.

Patients with known renal impairment or those taking nephrotoxic drugs should have their renal function assessed at the beginning of treatment and periodically thereafter. The risks and benefits of ROWASA should be carefully evaluated in these patients, and the medication should be discontinued if renal function deteriorates during therapy.

Hepatic failure is another serious concern; the risks and benefits of using ROWASA in patients with known liver impairment should be evaluated. Severe cutaneous adverse reactions may also occur, necessitating discontinuation of the medication at the first signs or symptoms of such reactions or other signs of hypersensitivity, with consideration for further evaluation.

Patients should be advised to avoid sun exposure if they have pre-existing skin conditions due to the risk of photosensitivity. Cases of nephrolithiasis have been reported with the use of mesalamine, and it is important to ensure adequate hydration during treatment, as mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT).

Furthermore, mesalamine may interfere with laboratory tests, leading to elevated urinary normetanephrine test results. Known or suspected hypersensitivity to salicylates, aminosalicylates, sulfites, or any other ingredients in ROWASA should be noted. Symptoms of salicylate toxicity include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication may result in electrolyte and blood pH imbalances and potentially affect other organs, including the kidneys and liver.

Reports from uncontrolled clinical studies and postmarketing surveillance indicate a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in patients aged 65 years or older receiving mesalamine-containing products like ROWASA compared to younger adult patients.

Drug Interactions

The concomitant use of nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs), may lead to an increased risk of nephrotoxicity. It is advisable to monitor renal function closely and observe for any mesalamine-related adverse reactions in patients receiving these medications.

Additionally, the use of azathioprine or 6-mercaptopurine in conjunction with this medication may elevate the risk of blood dyscrasias. Regular monitoring of complete blood cell counts and platelet counts is recommended to ensure patient safety and to detect any potential hematological complications early.

Packaging & NDC

The table below lists all NDC Code configurations of Rowasa (mesalamine), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Therefore, the use of this medication in children, infants, and adolescents should be approached with caution until further data is available.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, were not adequately represented in clinical trials of ROWASA, making it difficult to ascertain whether they respond differently compared to younger patients. However, reports from uncontrolled clinical studies and postmarketing surveillance indicate a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine-containing products such as ROWASA. This increased risk may be associated with factors such as ulcerative colitis, the use of interacting medications, or diminished renal function.

Given these considerations, it is advisable to monitor complete blood cell counts and platelet counts in elderly patients during treatment with ROWASA. Additionally, when prescribing ROWASA to this population, healthcare providers should take into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies. These factors may necessitate careful dose adjustments and enhanced monitoring to ensure patient safety.

Pregnancy

Published data from meta-analyses, cohort studies, and case series regarding the use of mesalamine during pregnancy have not consistently demonstrated an association between mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, it is important to note that adverse effects on maternal and fetal outcomes are associated with ulcerative colitis during pregnancy. Increased disease activity in women with ulcerative colitis has been linked to a higher risk of adverse pregnancy outcomes, including preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g), and small for gestational age infants at birth.

In animal reproduction studies, mesalamine was administered to rats and rabbits during organogenesis at oral doses up to 5 and 8 times the maximum recommended human dose, respectively, without revealing any evidence of harm to the embryo or fetus. Additionally, there is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk of major congenital malformations, including cardiac malformations.

The background risk of major birth defects and miscarriage for the indicated population remains unknown, as all pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2% to 4% and 15% to 20%, respectively.

It is essential to consider that published epidemiologic studies have important methodological limitations that may hinder the interpretation of the data. These limitations include the inability to control for confounders such as underlying maternal disease and concomitant medication use, as well as missing information regarding the dose and duration of mesalamine use. Therefore, healthcare professionals should weigh the potential benefits of mesalamine treatment against the risks associated with untreated ulcerative colitis during pregnancy.

Lactation

Data from published literature indicate that mesalamine and its metabolite, N‑acetyl‑5‑aminosalicylic acid, are present in human milk in small amounts. The relative infant doses (RID) for mesalamine are reported to be 0.1% or less. In lactation studies, maternal doses of mesalamine from various oral and rectal formulations ranged from 500 mg to 4.8 g daily. The average concentration of mesalamine in breast milk ranged from non‑detectable to 0.5 mg/L, while the average concentration of N‑acetyl‑5‑aminosalicylic acid ranged from 0.2 to 9.3 mg/L.

There have been case reports of diarrhea observed in breastfed infants exposed to mesalamine. However, there is no information available regarding the effects of mesalamine on milk production. The lack of clinical data during lactation prevents a clear determination of the risk of ROWASA to an infant during breastfeeding. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother’s clinical need for ROWASA and any potential adverse effects on the breastfed child from ROWASA or from the underlying maternal condition.

Caregivers should be advised to monitor breastfed infants for signs of diarrhea. Estimated daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day of mesalamine (RID 0% to 0.1%) and 0.03 to 1.4 mg/kg/day of N‑acetyl‑5‑aminosalicylic acid.

Renal Impairment

Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically during therapy. It is important to evaluate the risks and benefits of ROWASA in patients with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates while on therapy, ROWASA should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using ROWASA. It is essential to consider the degree of liver function compromise when determining the appropriateness of treatment. Monitoring of liver function may be necessary to ensure patient safety and to assess the need for any dosage adjustments. Healthcare providers are advised to exercise caution and to conduct a thorough assessment prior to initiating therapy in this population.

Overdosage

In the event of an overdose of ROWASA, which contains mesalamine, healthcare professionals should be aware of the potential symptoms and management strategies associated with salicylate toxicity.

Symptoms of salicylate toxicity may manifest as nausea, vomiting, and abdominal pain. Additional signs include tachypnea, hyperpnea, tinnitus, and various neurologic symptoms such as headache, dizziness, confusion, and seizures. In cases of severe intoxication, there is a risk of significant electrolyte and blood pH imbalances, which may lead to complications involving other organs, including renal and hepatic systems.

There is currently no specific antidote for mesalamine overdose. However, conventional treatment approaches for salicylate toxicity may be beneficial in managing acute overdosage. These approaches typically involve gastrointestinal decontamination to prevent further absorption of the drug.

It is crucial to address any fluid and electrolyte imbalances that may arise due to the overdose. This can be achieved through the administration of appropriate intravenous therapy, which also aids in maintaining adequate renal function. Continuous monitoring and supportive care are essential to ensure patient safety and recovery.

Nonclinical Toxicology

In a 2-year carcinogenicity study conducted in Wistar rats administered mesalamine at doses up to 320 mg/kg/day, which is approximately 0.78 times the maximum recommended human dose based on body surface area comparison, there was no observed increase in the incidence of neoplastic lesions compared to controls. Furthermore, mesalamine demonstrated no mutagenic potential in various Salmonella typhimurium tester strains (TA98, TA100, TA1535, TA1537, TA1538) and did not induce reverse mutations in an assay utilizing E. coli strain WP2UVRA. Additionally, there was no evidence of genotoxicity in an in vivo mouse micronucleus assay at a dose of 600 mg/kg or in an in vivo sister chromatid exchange assay at doses up to 610 mg/kg. Mesalamine also did not affect fertility in rats at doses up to 320 mg/kg/day.

Preclinical studies have identified the kidney as the primary target organ for mesalamine toxicity. Adverse changes in renal function were noted in rats following a single oral dose of 600 mg/kg, while no such effects were observed at a dose of 200 mg/kg. Gross kidney lesions, including papillary necrosis, were documented after a single oral dose exceeding 900 mg/kg and after intravenous doses greater than 214 mg/kg. Similar responses were noted in mice.

In a 13-week oral (gavage) dose study in rats, the high dose of 640 mg/kg/day resulted in fatalities likely due to renal failure, with dose-related renal lesions such as papillary necrosis and multifocal tubular injury observed in most rats receiving this high dose, as well as in males receiving a lower dose of 160 mg/kg/day. However, renal lesions were not present in the female rats receiving 160 mg/kg/day. Minimal tubular epithelial damage was noted in males at a dose of 40 mg/kg/day, which was reversible.

A six-month oral study in dogs established a no-observable adverse effect level for mesalamine at 40 mg/kg/day, while doses of 80 mg/kg/day and higher resulted in renal pathology consistent with that observed in rats. In a combined 52-week toxicity and 127-week carcinogenicity study in rats, degeneration of the kidneys was noted at doses of 100 mg/kg/day and above when administered in the diet for 52 weeks. After 127 weeks, there was an increased incidence of kidney degeneration and hyalinization of basement membranes and Bowman's capsule at doses of 100 mg/kg/day and above.

In a 12-month eye toxicity study in dogs, Keratoconjunctivitis Sicca (KCS) was observed at oral doses of 40 mg/kg/day and higher. The oral preclinical studies utilized a highly bioavailable suspension, facilitating absorption throughout the gastrointestinal tract.

Postmarketing Experience

During post-approval use of mesalamine, various adverse reactions have been reported voluntarily from a population of uncertain size. As a result, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders have included myocarditis and pericarditis.

Gastrointestinal Disorders reported include pancreatitis.

Hematologic Disorders encompass agranulocytosis, aplastic anemia, eosinophilia, leukopenia, neutropenia, pancytopenia, and thrombocytopenia.

Hepatic Disorders have involved elevated liver enzymes and hepatic failure.

Nervous System events include intracranial hypertension.

Renal and Urinary Disorders reported are acute renal failure, chronic renal failure, interstitial nephritis, nephrogenic diabetes insipidus, nephrolithiasis, and nephrotoxicity.

Additionally, urine discoloration has been observed ex-vivo due to contact of mesalamine, including its inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Reproductive System and Breast Disorders have included reversible oligospermia.

Respiratory, Thoracic, and Mediastinal Disorders reported are fibrosing alveolitis and pleurisy/pleuritis.

Skin and Subcutaneous Tissue Disorders have included AGEP, DRESS, and SJS/TEN.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, specifically the Instructions for Use, to ensure proper understanding of the medication. It is important to inform patients that ROWASA may decrease renal function, particularly in individuals with known renal impairment or those taking nephrotoxic drugs. Healthcare providers should emphasize the necessity of periodic monitoring of renal function during therapy and encourage patients to complete all blood tests as ordered.

Patients must be instructed to discontinue ROWASA and promptly report to their healthcare provider if they experience new or worsening symptoms indicative of acute intolerance syndrome, such as cramping, abdominal pain, bloody diarrhea, fever, headache, or rash. Additionally, patients with a history of liver disease should be advised to contact their healthcare provider if they notice any signs or symptoms of worsening liver function.

Healthcare providers should inform patients about the signs and symptoms of severe cutaneous adverse reactions. Patients should be instructed to stop taking ROWASA and report to their healthcare provider at the first appearance of any severe cutaneous adverse reaction or other signs of hypersensitivity.

For patients with pre-existing skin conditions, it is essential to advise them to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors to minimize the risk of skin reactions. Furthermore, patients should be instructed to maintain adequate fluid intake during treatment to reduce the risk of kidney stone formation. They should also be advised to contact their healthcare provider if they experience any signs or symptoms of a kidney stone, such as severe side or back pain or blood in the urine.

Storage and Handling

The product is supplied in a foil-wrapped unit containing seven bottles. Each bottle should be stored at a controlled room temperature of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C to 30°C (59°F to 86°F).

Once the foil-wrapped unit is opened, all enemas should be utilized promptly as directed by a physician. It is important to note that the contents of enemas removed from the foil pouch may darken over time. While slight darkening does not affect the potency of the product, enemas exhibiting dark brown contents should be discarded.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Rowasa as submitted by Viatris Specialty LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)