Salofalk

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SALOFALK® (SALOFALK®)

Composition:

Active substance: mesalazine (5-aminosalicylic acid);

1 suppository contains 250 mg of mesalazine;

Excipient: hard fat.

1 suppository contains 500 mg of mesalazine;

Excipients: hard fat, cetyl alcohol, sodium docosate.

Pharmaceutical form. Rectal suppositories.

Main physicochemical properties: white to cream-colored, torpedo-shaped suppositories with homogeneous consistency and smooth, unbroken surface. During storage, a white coating may form on the surface due to recrystallization of hard fats.

Pharmacotherapeutic group.

Gastrointestinal tract and metabolism. Antidiarrheals, intestinal anti-inflammatory/antimicrobial agents. Intestinal anti-inflammatory agents. Aminosalicylic acid and related agents. Mesalazine.

ATC code A07EC02.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

The mechanism of anti-inflammatory action is unknown. Results of in vitro studies suggest that inhibition of lipoxygenase may play a certain role.

An effect on prostaglandin concentrations in the intestinal mucosa has also been demonstrated. Mesalazine (5-aminosalicylic acid/5-ASCA) may also act as a scavenger of reactive oxygen species radicals.

After rectal administration, mesalazine acts predominantly locally on the intestinal mucosa and submucosal layers.

Pharmacokinetics.

General properties of mesalazine

Absorption

Absorption of mesalazine is highest in the proximal part of the intestine and lowest in the distal part.

Biological transformation

Mesalazine is metabolized both presystemically in the intestinal mucosa and in the liver to pharmacologically inactive N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Acetylation appears to be independent of the acetylation phenotype of the patient. Some acetylation also occurs due to bacterial activity in the colon. Protein binding of mesalazine and N-Ac-5-ASA is 43% and 78%, respectively.

Elimination/Excretion

Mesalazine and its metabolite N-Ac-5-ASA are excreted in feces (main portion), in urine (ranging between 20% and 50%, depending on the mode of administration, pharmaceutical form, and release mechanism of mesalazine) and in bile (minor portion). Renal excretion occurs predominantly as N-Ac-5-ASA. Approximately 1% of the total orally administered dose of mesalazine is excreted in breast milk, mainly as N-Ac-5-ASA.

Characteristics of Salofalk suppositories

Distribution

Scintigraphic studies with technetium-labeled Salofalk suppositories showed a peak distribution of the melted suppository at body temperature after 2–3 hours. The distribution is primarily confined to the rectum and rectosigmoid region. Therefore, Salofalk suppositories are particularly suitable for the treatment of proctitis (ulcerative colitis of the rectum).

Absorption

After both single administration and multi-week therapy with 500 mg mesalazine as Salofalk suppositories three times daily, peak plasma concentrations of 5-ASA ranged from 0.1 to 1.0 µg/mL, while the range for the main metabolite N-Ac-5-ASA was from 0.3 to 1.6 µg/mL. In some cases, peak plasma concentration of 5-ASA was reached within the first hour after administration.

Elimination

After single administration of 500 mg mesalazine as a Salofalk suppository, approximately 11% (within 72 hours), and after multi-week or long-term therapy with 500 mg mesalazine as Salofalk suppositories three times daily, approximately 13% of the administered dose of 5-ASA was excreted in urine. Approximately 10% of a single administered dose was excreted in bile.

Clinical characteristics.

Indications.

Salo-falk, 250 mg rectal suppositories

Treatment of acute episodes and maintenance of remission in ulcerative colitis limited to the rectum.

Salo-falk, 500 mg rectal suppositories

Treatment of acute episodes of ulcerative colitis limited to the rectum.

Contraindications.

Hypersensitivity to mesalazine, to any of the excipients or to salicylates; active peptic ulcer disease of the stomach or duodenum; severe hepatic and/or renal impairment; hemorrhagic diathesis.

Interaction with other medicinal products and other forms of interaction.

No specific studies on interactions with other medicinal products have been conducted.

When Salo-falk is used concomitantly with azathioprine, 6-mercaptopurine or thioguanine, possible enhancement of the myelosuppressive effect of azathioprine, 6-mercaptopurine or thioguanine should be considered.

There is evidence that mesalazine may reduce the anticoagulant effect of warfarin.

Special precautions for use.

At the physician’s discretion, blood tests (complete blood count; liver function tests such as ALT or AST; serum creatinine) and urine tests (dipstick testing, sediment) should be performed before and during treatment. Testing is generally recommended approximately 14 days after initiation of treatment, followed by 2–3 additional tests at 4-week intervals.

If test results are normal, routine monitoring may be performed every 3 months; however, if additional symptoms occur, tests should be performed urgently.

Mesalazine should be used with caution in patients with impaired liver function.

Mesalazine should not be used in patients with impaired renal function. Worsening renal function during treatment should raise suspicion of mesalazine-induced nephrotoxicity. In such cases, administration of Salofalk suppositories should be discontinued immediately.

Cases of nephrolithiasis, including formation of stones composed of 100% mesalazine, have been reported during mesalazine therapy. Adequate fluid intake should be ensured during treatment.

Mesalazine may cause red-brown discoloration of urine upon contact with sodium hypochlorite-based bleach (e.g., in toilets cleaned with sodium hypochlorite-containing bleaches).

Very rarely, severe blood dyscrasias associated with mesalazine use have been reported. Hematological investigations should be performed if patients develop unexplained bleeding, bruising, purpura, anemia, fever, or pharyngolaryngeal pain. Salofalk suppositories should be discontinued if blood dyscrasia is suspected or confirmed.

Rarely, hypersensitivity reactions affecting the heart (myocarditis and pericarditis) caused by mesalazine have been reported. In such cases, Salofalk suppositories should be discontinued immediately.

Patients with pulmonary disorders, particularly asthma, should be under medical supervision throughout the course of mesalazine treatment.

Serious skin reactions

Serious skin adverse reactions (SSARs), including drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported with mesalazine therapy. Mesalazine should be discontinued at the first appearance of signs or symptoms of serious skin reactions, such as skin rash, mucosal lesions, or any other signs of hypersensitivity.

Idiopathic intracranial hypertension

Idiopathic intracranial hypertension (pseudotumor cerebri) has been reported in patients taking mesalazine. Patients should be informed about the signs and symptoms of idiopathic intracranial hypertension, including severe or recurrent headache, visual disturbances, or tinnitus. If idiopathic intracranial hypertension occurs, discontinuation of mesalazine should be considered.

Patients with hypersensitivity reactions to drugs containing sulfasalazine should be under medical supervision from the beginning of treatment with mesalazine. If Salofalk suppositories cause acute intolerance symptoms such as seizures, acute abdominal pain, fever, severe headache, or rash, therapy should be discontinued immediately.

Cetyl alcohol, an excipient in Salofalk 500 mg suppositories, may cause local skin irritation (e.g., contact dermatitis).

Use during pregnancy or breastfeeding.

Pregnancy

There are no adequate data on the use of mesalazine in pregnant women. However, limited data from a small number of pregnant women suggest no adverse effects of mesalazine on pregnancy or fetal and/or neonatal health. To date, there are no other epidemiological data available for this drug. In only one case, neonatal renal failure was reported after prolonged use of high-dose mesalazine (2–4 g orally) during pregnancy.

Animal studies with oral mesalazine administration showed no direct or indirect adverse effects on pregnancy, embryonic/fetal development, parturition, or postnatal development.

Salofalk suppositories should be used during pregnancy only if the expected benefit outweighs the potential risk.

Breastfeeding

N-acetyl-5-aminosalicylic acid, and to a lesser extent mesalazine, are excreted in breast milk. Experience with use in breastfeeding women is currently limited. Hypersensitivity reactions in the breastfed infant, such as diarrhea, cannot be excluded. Therefore, Salofalk suppositories should be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the infant. If diarrhea develops in the breastfed infant, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Mesalazine has no effect or only a negligible effect on the ability to drive or operate machinery.

Dosage and Administration.

When using Salofalk suppositories, they should be administered rectally three times daily: in the morning, during the day, and in the evening before bedtime.

The desired therapeutic effect can only be achieved with regular and continuous use of Salofalk suppositories. The duration of treatment is determined by the physician.

Adults and elderly patients

Treatment of exacerbations of ulcerative colitis

Depending on individual clinical needs, 2 suppositories of Salofalk 250 mg or 1 suppository of Salofalk 500 mg should be administered rectally three times daily (equivalent to 1500 mg of mesalazine per day).

Maintenance of remission in ulcerative colitis

1 suppository of Salofalk 250 mg should be administered rectally three times daily (equivalent to 750 mg of mesalazine per day).

Children. There is insufficient data on the use of this medicinal product in children.

Overdose.

There have been rare reports of overdose (e.g., intentional self-poisoning with high oral doses of mesalazine), which did not indicate renal or hepatic toxicity. There is no specific antidote; treatment should be symptomatic and supportive.

Adverse reactions.

The following adverse reactions have been observed after administration of mesalazine:

*More detailed information is provided in the section "Special precautions for use".

Serious skin reactions have been reported, including drug-induced eosinophilia with systemic symptoms (DRESS syndrome), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), associated with mesalazine treatment (see section "Special precautions for use").

Photosensitivity

Severe reactions have been reported in patients with skin disorders such as atopic dermatitis and atopic eczema.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the use of this medicinal product. Healthcare professionals and patients, as well as patients' legal representatives, should report any suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Keep out of the reach of children. Store at a temperature not exceeding 30 °C. Store in the original packaging to protect from light.

Packaging: 5 suppositories per strip, 2 strips per cardboard box.

Prescription category. Prescription only.

Manufacturer.

Dr. Falk Pharma GmbH.

Manufacturer's address and location of operations.

Leinenweberstrasse 5, 79108 Freiburg Im Breisgau, Germany.