The half-life of (natural) somatostatine-14 is very short, about only 3 minutes. This means that its therapeutic effects diminish very rapidly and continuous intravenous infusion is required to keep somatostatine concentrations effective. The use of an intravenous rate controlling device like an infusion pump makes somatostatine administration tolerable, while rapid infusion would cause gastroenteric disorders. Toxicological studies carried out on mammals excluded relevant side-effects, while in vivo and in vitro tests highlighted no mitogenic activity. The administration of high and prolonged doses of somatostatine or somatostatine analogues may cause nausea, meteorism, abdominal pain or diarrhea, though these side-effects never get too severe and especially occur during the first drug administrations. They lessen with the course of treatment and disappear completely after one week, two at the maximum. In some cases sugar intolerance or hyperglycemia may occur due to the inhibitory effect of somatostatine and its analogues on insulin release, generally within tolerable and controllable limits. Gastric or intestinal stasis from reduced peristaltic activity has also been observed. A slight decrease in blood pressure or heart rate is definitely uncommon. In some cases somatostatine favored the formation of cholesterol gall stones in the gall bladder due to insufficient cholagogue activity resulting from reduction of cholecystokinin and enterohepatic circulation of bile salts. This may be prevented and kept under control by employing drugs having cholagogue and choleretic activity.

RETINOIDS
At the concentrations of the MDB vitamin compound, retinoids administered in usual dose levels of 90-100 mg per kg and per day, do not generally cause side-effects. In patients prone to hypertriglyceridemia an increase in blood triglycerides may occur, while patients suffering from hepatic-biliary insufficiency may experience side-effects in the gastro-enteric apparatus due to their difficulty in absorbing retinoids.

ASCORBIC ACID
Side-effects only occur in patients affected by gastritis or gastric ulcer, whereby administration of vitamin C is more advisable in effervescent tablets rather than in powder, in all cases during meals.

BROMOCRIPTINE
At usual dose levels of 2.5 mg per day, bromocriptine seldom causes side-effects, especially if administration is fractioned during the three main meals. Yet nausea occurs more frequently and may be kept under control by using antiemetic and antinausea drugs like chlorhydrate ondansetron, which is active and advisable in similar situations caused by somatostatin

CABERGOLINE
During the first days of treatment, vehicle driving or the operation of machinery should be very careful. Cabergoline may cause nausea and disturbances like dyspepsia and gastritis. Kidney or liver pain has not been observed nor confirmed. Chronic use of the drug may mildly lower blood pressure.

VITAMIN D
Its calcaemic effect may contraindicate or recommend limited use of vitamin D. Hence, during vitamin D administration blood calcium tests are recommended on a weekly basis at the initial stage of treatment, while subsequently these tests may be performed less frequently. As a rule, vitamin D administered at 8-10 drop doses in adults not cause blood calcaemia to exceed physiological levels.

CYCLOPHOSPHAMIDE
With 50 mg (max.100 mg) dose levels in MDB treatment some patients may experience a decrease in the number of red and white blood cells as well as platelets. The combination of melatonin, vitamin E and retinoids in the MDB therapy greatly reduces the effects of cyclophosphamide. In case of anemia erythropoietin at 2,000 to 10,000 unit dose levels may be infused depending on level and severity of anemia. Erythropoietin infusion may be intravenous or subcutaneous. In case of WBC deficiency (leucopenia) drugs like cytokines (Granulokine) which raise granulocyte blood levels are useful. Because melatonin is atoxic, even much higher doses have positive effects in case of anemia, as well as leucopenia or platelet deficiency.

HYDROXYUREA
Its negative effects are comparable to those induced by cyclophosphamide and may be kept under control with the same drugs: erythropoietin, granulokin, melatonin. In MBD treatment, drug dose levels – hence side-effects – are dramatically reduced as opposed to conventional protocols. The employment of hydroxyurea is especially indicated in treating brain tumors as it is capable of crossing the brain blood barrier.

MELATONIN
Studies performed on healthy volunteers, laboratory animals and in vitro have excluded damage caused by this drug. Even hundredfold higher doses than those usually employed in treatment have caused no side effects either concomitant or subsequent to administration, as much was evidenced by monitoring patients even for several years. The only inconvenience observed, especially during the first administrations, is induction of drowsiness to markedly variable extent depending on patient.