Sfrowasa

Description

The active ingredient in sfROWASA (mesalamine) Rectal Suspension is mesalamine, also known as 5-aminosalicylic acid (5-ASA). Chemically, mesalamine is 5-amino-2-hydroxybenzoic acid, with an empirical formula of C7H7NO3 and a molecular weight of 153.14. sfROWASA is supplied as a suspension for rectal administration, with each rectal suspension unit containing 4 grams of mesalamine. The inactive ingredients include carbomer 934P, edetate disodium, potassium acetate, purified water, sodium benzoate, and xanthan gum, with sodium benzoate serving as a preservative.

Uses and Indications

sfROWASA is an aminosalicylate 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 sfROWASA (mesalamine) rectal suspension is one rectal instillation of 4 grams, administered once daily. It is preferable to administer the dose at bedtime, allowing the medication to be retained for approximately eight hours. The duration of treatment may range from 3 to 6 weeks, depending on the patient's symptoms and sigmoidoscopic findings.

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

Contraindications

Use of sfROWASA is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, 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

Renal function should be assessed at the initiation of treatment with sfROWASA and monitored periodically throughout the course of therapy. It is essential to evaluate the risks and benefits of administering sfROWASA in patients with known renal impairment or those concurrently taking nephrotoxic medications. Should renal function deteriorate during treatment, discontinuation of sfROWASA is warranted.

In cases where mesalamine-induced acute intolerance syndrome is suspected, characterized by symptoms such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash, treatment should be discontinued immediately.

For patients with known liver impairment, a careful assessment of the risks and benefits of using sfROWASA is necessary. Additionally, any signs or symptoms indicative of severe cutaneous adverse reactions or other hypersensitivity reactions should prompt immediate discontinuation of the medication and consideration for further evaluation.

Patients should be advised to avoid sun exposure if they have pre-existing skin conditions, as photosensitivity may occur. Furthermore, there have been reports of nephrolithiasis associated with mesalamine use. It is important to note that mesalamine-containing stones are not detectable through standard radiography or computed tomography (CT). Therefore, ensuring adequate hydration during treatment is crucial to mitigate this risk.

Healthcare professionals should be aware that mesalamine may interfere with laboratory tests, specifically leading to elevated urinary normetanephrine test results. Regular monitoring of renal function is implied for patients receiving sfROWASA, although no specific laboratory tests are mandated.

In summary, healthcare providers must remain vigilant for signs of acute intolerance syndrome and severe cutaneous adverse reactions, and take appropriate action by discontinuing treatment and consulting with the patient’s physician as necessary.

Side Effects

Patients receiving sfROWASA may experience a range of adverse reactions. The most common adverse reactions, occurring in 1% or more of patients, include gas/flatulence, flu, fever, leg/joint pain, hemorrhoids, rectal pain, and hair loss.

Serious adverse reactions have been identified, necessitating careful monitoring and management. Patients with renal impairment should have their renal function assessed at the beginning of treatment and periodically thereafter. It is crucial to evaluate the risks and benefits of sfROWASA in these patients or those taking nephrotoxic drugs, and to discontinue therapy if renal function deteriorates.

Mesalamine-induced acute intolerance syndrome is another serious concern; treatment should be discontinued if symptoms such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, or rash are suspected. Additionally, patients with known liver impairment should be evaluated for the risks and benefits of using sfROWASA, as hepatic failure has been reported.

Severe cutaneous adverse reactions may occur, and treatment should be stopped at the first signs or symptoms of such reactions or any other signs of hypersensitivity. Patients are also advised to avoid sun exposure if they have pre-existing skin conditions due to the risk of photosensitivity.

Nephrolithiasis has been reported in patients using mesalamine, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to mitigate this risk.

Furthermore, mesalamine may interfere with laboratory tests, leading to elevated urinary normetanephrine test results. Patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or any other ingredients in sfROWASA should not use this medication. Symptoms of salicylate toxicity, which include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (such as headache, dizziness, confusion, and seizures), should be monitored closely, as severe intoxication may result in electrolyte and blood pH imbalances and potential organ involvement.

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 sfROWASA compared to younger adult patients.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Sfrowasa (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, as there is insufficient data to support its use in these populations. Healthcare professionals are advised to consider this lack of established safety and efficacy when making treatment decisions for pediatric patients.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, were not adequately represented in clinical trials of sfROWASA, 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 sfROWASA. 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 patients aged 65 years and older during treatment with sfROWASA. Additionally, when prescribing sfROWASA to elderly patients, healthcare providers should take into account the higher 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 evaluation and potential dose adjustments to ensure the safety and efficacy of treatment in this population.

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.

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. Despite this, the background risk of major birth defects and miscarriage in the indicated population remains unknown. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes, with the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies in the U.S. general population being 2% to 4% and 15% to 20%, respectively.

In women with ulcerative colitis, increased disease activity has been linked to a higher risk of adverse pregnancy outcomes, which may include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g), and small for gestational age infants at birth. Furthermore, the available data suggest that mesalamine exposure during early pregnancy (first trimester) and throughout pregnancy does not appear to be associated with an increased risk of major congenital malformations, including cardiac malformations.

Healthcare professionals should consider these factors when prescribing mesalamine to pregnant patients or women of childbearing potential.

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. The average concentration of mesalamine in breast milk ranges from non-detectable to 0.5 mg/L, while the average concentration of N‑acetyl‑5‑aminosalicylic acid ranges from 0.2 to 9.3 mg/L. Estimated daily dosages for an exclusively breastfed infant are 0 to 0.075 mg/kg/day for mesalamine (RID 0% to 0.1%) and 0.03 to 1.4 mg/kg/day for N‑acetyl‑5‑aminosalicylic acid.

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 limits the ability to clearly determine the risk of sfROWASA to an infant during breastfeeding. Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for sfROWASA and any potential adverse effects on the breastfed child from sfROWASA or from the underlying maternal condition.

Healthcare providers are advised to instruct caregivers to monitor breastfed infants for signs of diarrhea.

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 sfROWASA in patients with known renal impairment or those taking nephrotoxic drugs. If renal function deteriorates while on therapy, sfROWASA should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits of using sfROWASA. Due to the potential for altered pharmacokinetics in this population, it is essential to consider the degree of liver function compromise when determining the appropriateness of therapy. Monitoring of liver function tests may be warranted to assess the impact of treatment and to ensure patient safety. Adjustments to dosing or treatment regimens may be necessary based on the severity of hepatic impairment, and ongoing assessment is recommended throughout the course of therapy.

Overdosage

In cases of mesalamine overdosage, healthcare professionals should be vigilant for symptoms indicative of salicylate toxicity. These symptoms may include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, headache, dizziness, confusion, and seizures.

Severe intoxication with salicylates can result in significant complications, including electrolyte and blood pH imbalances, which may lead to renal and liver involvement. Therefore, prompt recognition and management of these symptoms are critical.

There is currently no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may provide beneficial effects in acute cases. In instances of overdose, gastrointestinal tract decontamination may be necessary to prevent further absorption of the drug.

Management should also focus on correcting fluid and electrolyte imbalances. This can be achieved through the administration of appropriate intravenous therapy, ensuring that renal function remains adequate throughout the treatment process. Continuous monitoring and supportive care are essential to mitigate the risks associated with salicylate toxicity.

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.

Mesalamine has been shown to be non-mutagenic in various assays. It did not induce mutations in Salmonella typhimurium tester strains (TA98, TA100, TA1535, TA1537, TA1538) and did not produce reverse mutations in an assay using 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. Furthermore, mesalamine 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 changes were observed at a dose of 200 mg/kg. Gross kidney lesions, including papillary necrosis, were evident after a single oral dose exceeding 900 mg/kg and after intravenous doses greater than 214 mg/kg. Similar responses were observed in mice.

In a 13-week oral (gavage) 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. No renal lesions were noted in female rats at the 160 mg/kg/day dose, while minimal tubular epithelial damage was reversible in males at the 40 mg/kg/day dose.

A six-month oral study in dogs established a no-observable adverse effect level of 40 mg/kg/day, with doses of 80 mg/kg/day and higher leading to renal pathology similar to that seen 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 after 52 weeks, with an increased incidence of kidney degeneration and hyalinization of basement membranes and Bowman's capsule observed at the same doses after 127 weeks.

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

Postmarketing Experience

No specific postmarketing experience details are available in the provided text. As such, there are no reported adverse events or case reports to summarize.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Instructions for Use) thoroughly. It is important to inform them that sfROWASA may decrease renal function, particularly in individuals with known renal impairment or those taking nephrotoxic drugs. Periodic monitoring of renal function will be conducted during therapy, and patients should be encouraged to complete all blood tests ordered by their healthcare provider.

Patients must be instructed to discontinue sfROWASA and report to their healthcare provider if they experience new or worsening symptoms of acute intolerance syndrome, which may include cramping, abdominal pain, bloody diarrhea, fever, headache, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity. Those with known liver disease should be advised to contact their healthcare provider if they notice signs or symptoms indicative of worsening liver function.

It is essential to inform patients about the signs and symptoms of severe cutaneous adverse reactions. They should be instructed to stop taking sfROWASA and report to their healthcare provider at the first appearance of any severe cutaneous adverse reaction or other signs of hypersensitivity. Patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

Patients should be instructed to maintain adequate fluid intake during treatment to minimize the risk of kidney stone formation. They should contact their healthcare provider if they experience signs or symptoms of a kidney stone, such as severe side or back pain or blood in the urine. Elderly patients and those taking azathioprine or 6-mercaptopurine should be informed of the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. They should also be encouraged to complete all blood tests ordered by their healthcare provider.

Patients should be made aware that sfROWASA may cause staining of direct contact surfaces, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Therefore, it is advisable to administer the product in a suitable location. They should be instructed to shake the bottle to ensure the suspension is homogeneous and to remove the protective sheath from the applicator tip.

For administration, patients should be guided to lie on their left side with the lower leg extended and the upper right leg flexed forward for balance, or alternatively, to assume the knee-chest position. They should gently insert the applicator tip into the rectum, pointing toward the umbilicus, and steadily squeeze the bottle to discharge the medication. It is recommended that patients administer the medication at bedtime with the objective of retaining it throughout the night.

Patients should also be informed that their urine may become discolored reddish-brown while taking sfROWASA when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. If discolored urine is observed, they should monitor their urine flow and report to their healthcare provider only if the urine is discolored upon leaving the body, before contact with any surface or water (e.g., in the toilet).

Storage and Handling

The product is supplied in a foil-wrapped unit containing seven bottles. Each bottle must 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 suspensions should be utilized promptly as directed by the physician. It is important to note that the contents of suspensions removed from the foil pouch may darken over time. While slight darkening does not affect the potency of the product, any suspensions 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 Sfrowasa as submitted by Viatris Specialty LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)