Asacol Enema

ASACOL ENEMA is used for the treatment and maintenance of remission in ulcerative colitis.

Posology
Adult dose: Two gram administered at night per rectum.
Method of administration
Rectal use.
Before using the enema: The bottle should be warmed to body temperature in a basin or bowl of warm water for about 10 minutes. The bottle should be shaken well immediately before inserting the enema.
Inserting the enema: The screw cap must be twisted off from the bottle and the applicator tip must be twisted on. The applicator tip can be lubricated with vaseline. For the enema administration the patient should lie on the left side with the left leg extended and the right leg bent. After inserting the applicator tip into the rectum the liquid should be pressed out gently and slowly. The tip should be withdrawn with the container still compressed. The patients should try to stay in the administration position for 5 to 10 minutes or until the urge to pass the enema has disappeared. The enema should be retained in the bowel if possible without evacuation of the bowels until the next morning.

Hypersensitivity to mesalazine or to any of the excipients (see section 6.1).
History of allergy to salicylates.
Severe liver impairment.
Severe renal impairment (GFR less than 30 ml per minute).
Safety in pregnancy and lactation has not been established.
Safety and efficacy have not been established in children.

Blood tests (differential blood count, liver function parameters such as ALT or AST; serum creatinine) and urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating medical practitioner. As a guideline, follow-up tests are recommended 14 days after commencement of treatment and then every 4 weeks for the following 12 weeks. If the findings are normal, follow-up tests should be carried out every three months. If additional signs appear, these tests should be performed immediately.
Renal impairment
Caution should be exercised in patients with impaired renal function raised serum creatinine or proteinuria. The possibility of mesalazine-induced nephrotoxicity, which may be reversible on withdrawal, should be suspected in patients developing renal failure during treatment. Treatment with ASACOL ENEMA should be stopped immediately if there is evidence of renal impairment and patients should seek immediate medical advice.
Serious skin side effects
Serious cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with ASACOL ENEMA treatment. ASACOL ENEMA must be discontinued at the first appearance of symptoms of serious skin adverse reactions such as skin rash, mucosal lesions or any other sign of hypersensitivity.
Nephrolithiasis
Cases of nephrolithiasis have been reported with the use of ASACOL ENEMA including stones with a 100 % mesalazine content. It is recommended to ensure adequate fluid intake during treatment.
Hepatic impairment
There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if ASACOL ENEMA is administered to patients with liver impairment (see section 4.3).
Blood dyscrasia
Serious blood dyscrasia has been reported. Patients should be monitored with care to avoid blood dyscrasia resulting from developing bone marrow depression. Haematological investigations including a complete blood count should be performed prior to initiation and whilst on therapy. Such tests are generally recommended within 14 days of initiation of therapy with 2 to 3 repeat tests each after another 4 weeks. If the results are normal, tests are recommended quarterly. In case additional signs of illness appear, further control tests are necessary. This procedure is to be followed, especially if a patient develops signs and symptoms suggestive of blood dyscrasia during treatment, such as unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat. Treatment with ASACOL ENEMA should be stopped immediately if there is a suspicion or evidence of blood dyscrasia (signs of unexplained bleeding, bruising, purpura, anaemia, persistent or sore throat) and patients should seek immediate medical advice.
Lung function impairment
In case of lung function impairment, especially asthma, patients need to be monitored very closely.
Cardiac hypersensitivity reactions
Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported rarely with ASACOL ENEMA. In case of suspected mesalazine-induced cardiac hypersensitivity ASACOL ENEMA must not be reintroduced. Caution should be used in patients with previous myo- or pericarditis of allergic background regardless of its origin.
Hypersensitivity to sulphasalazine
In patients with a history of hypersensitivity to sulphasalazine, therapy should be initiated only under close medical supervision. Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache or rash.
Gastric and duodenal ulcers
In case of existing gastric or duodenal ulcers, treatment should begin with caution based on theoretical grounds.
Geriatric patients
Use in the elderly should be handled with caution and ASACOL ENEMA should only be prescribed to patients having a normal or non-severely impaired renal and hepatic function. Co-administration of immunosuppressive medicines such as azathioprine or 6-MP can precipitate leucopoenia (see section 4.5). Concurrent use of NSAIDs or azathioprine may increase the risk of renal reactions (see section 4.5).
Excipients
ASACOL ENEMA contains 100 mg of sodium benzoate per dose, equivalent to 100 mg/100 ml. Sodium benzoate may cause non-immunological immediate contact reactions by a possible cholinergic mechanism.

No interaction studies have been performed. There is weak evidence that ASACOL ENEMA might decrease the anticoagulant effect of warfarin. ASACOL ENEMA can increase the myelosuppressive effects of azathioprine and 6-mercaptopurine or thioguanine. As a result, life-threatening infection can occur. Patients should be closely observed for signs of infection and myelosuppression. Haematological parameters, especially the leucocyte, thrombocyte, and lymphocyte cell counts should be monitored regularly (weekly), especially at initiation of such combination therapy, see section 4.4. If white blood cells are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by monitoring in 3 months intervals appears to be justified. Concurrent use of nephrotoxic medicines, such as NSAIDs or azathioprine may increase the risk of renal adverse reactions (see section 4.4).

Pregnancy
Safety in pregnancy has not been established.
Lactation
Low concentrations of mesalazine and its N-acetyl metabolite have been detected in human breast milk. Safety in lactation has not been established.
Fertility
No effects on fertility have been observed.

ASACOL ENEMA has no or negligible influence on the ability to drive and use machines.

a) Summary of the safety profile
Organ specific allergic reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported. Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.
Serious cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with ASACOL ENEMA treatment (see section 4.4). Side effects are presented by system organ class according to the following frequencies: Very common: u2265 10 % patients; common: u2265 1 % and < 10 % patients; uncommon: u2265 0,1 % and < 1 % patients; rare: u2265 0,01 % and < 0,1 % patients. The only common undesirable side effects were medicine ineffective (3,0 %) and flatulence (1,5 %).
b) Tabulated summary of adverse reactions

In case of accidental oral ingestion symptoms of overdosage include that of salicylism, e.g. dizziness, tinnitus, deafness, sweating, nausea and vomiting, headache, mental confusion, hyperventilation, fever, restlessness, ketosis, respiratory alkalosis and metabolic acidosis. Depression of the central nervous system may lead to coma, cardiovascular collapse and respiratory failure. There is no specific treatment for overdosage of ASACOL ENEMA but early lavage is recommended, if accidentally taken by mouth. Treatment is symptomatic and supportive.