1. Name Of The Medicinal Product
Salofalk 1g Suppositories
2. Qualitative And Quantitative Composition
Each suppository contains 1 g mesalazine.
For a full list of excipients, see section 6.1
3. Pharmaceutical Form
Suppositories
Appearance: light beige coloured, torpedo-shaped suppositories
4. Clinical Particulars
4.1 Therapeutic Indications
Treatment of acute mild to moderate ulcerative colitis that is limited to the rectum (ulcerative proctitis).
4.2 Posology And Method Of Administration
Adults and elderly:
One Salofalk 1g Suppository once daily (equivalent to 1g mesalazine daily) inserted into the rectum.
Children
There is little experience and only limited documentation for an effect in children.
General instructions for use:
Salofalk 1g Suppositories should be administered preferably at bedtime.
Treatment with Salofalk 1g Suppositories must be administered regularly and consistently, because only in this way can healing be successfully achieved.
The duration of use is determined by the physician.
4.3 Contraindications
Salofalk 1g Suppositories are contraindicated in patients with:
- known hypersensitivity to salicylates or the excipient
- severe impairment of hepatic or renal function
4.4 Special Warnings And Precautions For Use
Blood tests (differential blood count; liver function tests such as ALT or AST; serum creatinine) and dip-stick urinalysis should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, further testing is recommended 14 days after commencement of treatment, then a further two to three times at intervals of 4 weeks.
If the findings are normal, further testing should be carried out every 3 months. If additional symptoms occur, tests should be performed immediately.
Caution is recommended in patients with impaired hepatic function.
Salofalk 1g Suppositories are not recommended in patients with impaired renal function. Mesalazine-induced renal toxicity should be considered if renal function deteriorates during treatment.
Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment with Salofalk 1g Suppositories.
Patients with a history of adverse drug reactions to preparations containing sulphasalazine should be kept under close medical surveillance on commencement of a course of treatment with Salofalk 1g Suppositories. Should Salofalk 1g Suppositories cause acute intolerability reactions such as cramps, acute abdominal pain, fever, severe headache and rash, therapy should be discontinued immediately.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Specific interaction studies have not been performed.
Interactions may occur during treatment with Salofalk 1g Suppositories and concomitant administration of the following medicinal products. Most of these possible interactions are based on theoretical reasons:
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In patients who are concomitantly treated with azathioprine or 6-mercaptopurine, possible enhanced myelosuppressive effects of azathioprine or 6-mercaptopurine should be taken into account.
4.6 Pregnancy And Lactation
There are no adequate data from the use of Salofalk 1g Suppositories in pregnant women. However, data on a limited number of exposed pregnancies indicate no adverse effect of mesalazine on pregnancy or on the health of the fetus/newborn child. To date no other relevant epidemiologic data are available. In one single case after long-term use of a high dose mesalazine (2-4 g, orally) during pregnancy, renal failure in a neonate was reported.
Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.
Salofalk 1g Suppositories should only be used during pregnancy if the potential benefit outweighs the possible risk.
N-acetyl-5-aminosalicylic acid and to a lesser degree mesalazine are excreted in breast milk. Only limited experience during lactation in women is available to date. Hypersensitivity reactions like diarrhea can not be excluded. Therefore, Salofalk 1g Suppositories should only be used during breast-feeding if the potential benefit outweighs the possible risk. If the suckling neonate develops diarrhea, the breast-feeding should be discontinued.
4.7 Effects On Ability To Drive And Use Machines
No effects on ability to drive and use machines have been observed
4.8 Undesirable Effects
In clinical studies involving 248 participants, approximately 3% experienced adverse reactions while receiving Salofalk 1g Suppositories. The most commonly reported ADRs were headache, in approximately 0.8%, and gastrointestinal side effects (constipation in approximately 0.8%; nausea, vomiting and abdominal pain in 0.4% each).
The following side effects have been reported with the use of mesalazine:
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4.9 Overdose
No cases of intoxication have been reported to date and no specific antidotes are known.
If necessary, intravenous infusion of electrolytes (forced diuresis) should be considered in cases of overdose.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Aminosalicylic acid and similar agents
ATC code: A07EC02
The mechanism of the anti-inflammatory action is unknown. The results of in vitro studies indicate that inhibition of lipoxygenase may play a role.
Effects on prostaglandin concentrations in the intestinal mucosa have also been demonstrated. Mesalazine (5-Aminosalicylic acid / 5-ASA) may also function as a radical scavenger of reactive oxygen compounds.
On reaching the intestinal lumen, rectally administered mesalazine has largely local effects on the intestinal mucosa and submucosal tissue.
Clinical efficacy and safety of Salofalk® 1 g suppositories was evaluated in a multicentre phase III study, which included 403 patients with endoscopically and histologically confirmed mild to moderately active ulcerative proctitis. The mean disease activity index (DAI) at base line was 6.2 ± 1.5 (range: 3 – 10). Patients were randomised to treatment with one Salofalk® 1 g suppository (1 g OD group) or 3 suppositories containing 0.5 g mesalazine (0.5 g TID group per day for 6 weeks. The primary efficacy variable was clinical remission defined as DAI < 4 at the final visit or withdrawal. At the final per protocol analysis, 87.9% of the patients in the 1 g OD group and 90.7% of the 0.5 g TID group were in clinical remission (Intention-to-treat analysis: 1 g OD group: 84.0%; 0.5 g TID group: 84.7%). The mean change in DAI from baseline was -4.7 in both treatment groups. No drug-related serious AEs occurred.
5.2 Pharmacokinetic Properties
General considerations of mesalazine:
Absorption:
Mesalazine absorption is highest in proximal gut regions and lowest in distal gut areas.
Biotransformation:
Mesalazine is metabolised both pre-systemically by the intestinal mucosa and in the liver to the pharmacologically inactive N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). The acetylation seems to be independent of the acetylator phenotype of the patient. Some acetylation also occurs through the action of colonic bacteria. Protein binding of mesalazine and N-Ac-5-ASA is 43% and 78%, respectively.
Elimination:
Mesalazine and its metabolite N-Ac-5-ASA are eliminated via the faeces (major part), renally (varies between 20 and 50 %, dependent on kind of application, pharmaceutical preparation and route of mesalazine release, respectively), and biliary (minor part). Renal excretion predominantly occurs as N-Ac-5-ASA. About 1 % of total orally administered mesalazine dose is excreted into the breast milk mainly as N-Ac-5-ASA.
Salofalk 1g suppositories specific:
Distribution:
Scintigraphic studies with a similar medicinal product, technetium-labelled mesalazine 500mg suppositories showed peak spread of the suppository that had melted due to body temperature after 2 – 3 hours. The spread was limited primarily to the rectum and rectosigmoid junction. It is assumed that Salofalk 1g suppositories act very similar and thus are particularly suitable for treating proctitis (ulcerative colitis of the rectum).
Absorption:
In healthy subjects mean peak plasma concentrations of 5-ASA after a single rectal dose of 1g mesalazine (Salofalk 1 g Suppository) were 192 ± 125 ng/ml (range 19 – 557 ng/ml), those of the main metabolite N-Ac-5-ASA were 402 ± 211 ng/ml (range 57 – 1070 ng/ml). Time to reach the peak plasma concentration of 5-ASA was 7.1 ± 4.9 h (range 0.3 – 24 h).
Elimination:
In healthy subjects, after a single rectal dose of 1g mesalazine (Salofalk 1g Suppository) approx. 14 % of the administered 5-ASA dose were recovered in the urine during 48 hours.
5.3 Preclinical Safety Data
With the exception of a local tolerance study in dogs, which demonstrated good rectal tolerance, no preclinical studies have been performed with Salofalk 1g Suppositories.
Preclinical data on mesalazine reveal no special hazard for humans based on conventional studies of safety pharmacology, genotoxicity, carcinogenicity (rat) or toxicity to reproduction.
Kidney toxicity (renal papillary necrosis and epithelial damage in the proximal convoluted tubule or the whole nephron) has been seen in repeat-dose toxicity studies with high oral doses of mesalazine. The clinical relevance of this finding is unknown.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Hard fat
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
3 years
6.4 Special Precautions For Storage
Store in the original container in order to protect contents from light.
Do not store above 25°C.
6.5 Nature And Contents Of Container
Container (strip): PVC/polyethylene film
Package sizes: 10, 12, 15, 20, 30, 60, 90
Not all package sizes may be marketed.
6.6 Special Precautions For Disposal And Other Handling
Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing Authorisation Holder
Dr. Falk Pharma GmbH
Leinenweberstr. 5
79108 Freiburg
Germany
Tel: +49 (0)761 1514-0
8. Marketing Authorisation Number(S)
PL 08637/0018; PA573/4/4
9. Date Of First Authorisation/Renewal Of The Authorisation
17 May 2010
10. Date Of Revision Of The Text
17 May 2010
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