Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

It is strongly recommended that every time Gattex is administered to a patient, the name and lot number of the product are recorded in order to maintain a link between the patient and the lot of the product.

Adults

Colo-rectal polyps
A colonoscopy with removal of polyps should be performed at the time of starting treatment with Gattex. Once yearly follow-up colonoscopies (or alternate imaging) are recommended during the first 2 years of Gattex treatment. Subsequent colonoscopies are recommended at a minimum of five year intervals. An individual assessment whether increased frequency of surveillance is necessary should be performed based on the patient characteristics (e.g., age, underlying disease). See also section 5.1.
If a polyp is found, adherence to current polyp follow-up guidelines is recommended. In case of malignancy, Gattex therapy should be discontinued (see section 4.3).

Gastrointestinal neoplasia including hepatobiliary tract
In the rat carcinogenicity study, benign tumours were found in the small bowel and the extrahepatic bile ducts. These observations were not confirmed in clinical studies of more than one year duration. If 

a neoplasia is detected, it should be removed. In case of malignancy, Gattex treatment must be discontinued (see sections 4.3 and 5.3).

Gallbladder and bile ducts
Cases of cholecystitis, cholangitis, and cholelithiasis have been reported in clinical studies. In case of gallbladder or bile duct-related symptoms, the need for continued Gattex treatment should be reassessed.

Pancreatic diseases
Pancreatic adverse events such as chronic and acute pancreatitis, pancreatic duct stenosis, pancreas infection and increased blood amylase and lipase have been reported in clinical studies. In case of pancreatic adverse events, the need for continued Gattex treatment should be reassessed.

Monitoring of small bowel, gallbladder and bile ducts, and pancreas
SBS patients are to be kept under close surveillance according to clinical treatment guidelines. This usually includes the monitoring of small bowel function, gallbladder and bile ducts, and pancreas for signs and symptoms, and, if indicated, additional laboratory investigations and appropriate imaging techniques.

Intestinal obstruction
Cases of intestinal obstruction have been reported in clinical studies. In case of recurrent intestinal obstructions, the need for continued Gattex treatment should be reassessed.

Fluid overload and electrolyte balance
To avoid fluid overload or dehydration, careful adjustment of parenteral support is required in patients taking Gattex. Electrolyte balance and fluid status should be carefully monitored throughout treatment, especially during initial therapeutic response and discontinuation of Gattex treatment.

Fluid overload
Fluid overload has been observed in clinical trials. Fluid overload adverse events occurred most frequently during the first 4 weeks of therapy and decreased over time.

Due to increased fluid absorption, patients with cardiovascular disease, such as cardiac insufficiency and hypertension, should be monitored with regard to fluid overload, especially during initiation of therapy. Patients should be advised to contact their physician in case of sudden weight gain, face swelling, swollen ankles and/or dyspnoea. In general, fluid overload can be prevented by appropriate and timely assessment of parenteral nutrition needs. This assessment should be conducted more frequently within the first months of treatment.

Congestive heart failure has been observed in clinical trials. In case of a significant deterioration of the cardiovascular disease, the need for continued treatment with Gattex should be reassessed.

Dehydration
Patients with SBS are susceptible to dehydration that may lead to acute renal failure.
In patients receiving Gattex, parenteral support should be reduced carefully and should not be discontinued abruptly. The patient’s fluid status should be evaluated following parenteral support reduction and corresponding adjustment performed, as needed.

Concomitant medicinal product
Patients receiving oral concomitant medicinal products requiring titration or with a narrow therapeutic index should be monitored closely due to potential increased absorption (see section 4.5).

Special clinical conditions
Gattex has not been studied in patients with severe, clinically unstable concomitant diseases, (e.g., cardiovascular, respiratory, renal, infectious, endocrine, hepatic, or CNS), or in patients with malignancies within the last five years (see section 4.3). Caution should be exercised when prescribing Gattex.


Hepatic impairment
Gattex has not been studied in patients with severe hepatic impairment. The data from use in subjects with moderate hepatic impairment do not suggest a need for restricted use.

Discontinuation of treatment
Due to the risk of dehydration, discontinuation of treatment with Gattex should be managed carefully.

Important information about some of the ingredients:
Gattex contains less than 1 mmol sodium (23 mg) per dose. This means that it is essentially ‘sodium- free’.

Caution is needed when administering Gattex to persons with a known hypersensitivity to tetracycline (see section 4.3).

Paediatric population
See also general precautions for adults under this section.

Colo-rectal polyps/Neoplasia
Prior to initiating treatment with Gattex, faecal occult blood testing should be performed in all children. Subsequent testing should be conducted annually in children while they are receiving Gattex.

Prior to initiating treatment with Gattex, children 12 years of age and older should undergo a colonoscopy/sigmoidoscopy, unless one has been done within the past year. Children under 12 years of age should also have the procedure if they have unexplained blood in their stool. Colonoscopy is recommended for all children after one year of treatment, and at least every 5 years thereafter of continuous treatment with Gattex.

Effects on Driving

4.7   Effects on ability to drive and use machines

Gattex has minor influence on the ability to drive and use machines. However, cases of syncope have been reported in clinical studies (see section 4.8). Such events might impact the ability to drive and use machines.