Deferasirox

When ATH:
V03AC03

Pharmacological action

The complexing ligand triple, with high affinity for Fe3 and connecting it in the ratio 2:1. The drug increases the excretion of iron mainly with feces. It has a low affinity for Zn2 and Cu2 and reducing their concentration in the blood.

Pharmacokinetics.

Well absorbed after oral administration. The absolute bioavailability - about 70%. The bioavailability is increased by 13-25% at the reception for 30 minutes before meals with normal or high fat. Bioavailability in adolescents (12-17 Years) and children (2-12 Years) after single and multiple dose below, than in adults (in children under 6 years 50%). TCmax 1,5-4. The volume of distribution in adults - about 14 l. Contact proteins - 99%. It is metabolized by glyukuronirovaniya via UGT1A1, UGT1A3, CYP450 (about 8%). In the intestine occurs deconjugation and subsequent reabsorption (enterohepatic circulation). T1/2 — 8–16 ч. Write mainly in the faeces (84%) and to a lesser extent - in the urine (8%).

Testimony.

Chronic post-transfusion iron overload in adults and children older than 2 some years after transfusion 20 units (100 ml / kg) RBC and more or the presence of clinical data, indicating the development of chronic iron overload (incl. with an increase in serum ferritin more 1000 ug / l).

Dosage regimen

Inside, fasting (for 30 minutes before eating), 1 once daily at approximately the same time. The initial dose - 20 mg / kg / day. The recommended initial dose for patients, receiving more than 14 ml / kg / month of packed red cells (approximately more than 4 transfusions per month for adults) - 30 mg / kg, receiving less 7 ml / kg / month of packed red cells (less than about 2 blood transfusions per month for adults) - 10 mg / kg.

In patients with a good clinical effect during the treatment with deferoxamine initial dose should be 1/2 the previously used dose deferoxamine. Dose adjustment is carried out every 3-6 months (under the control of serum ferritin levels) speed, 5-10 mg / kg. If serum ferritin concentration is significantly lower 500 ug / l, should stop drug treatment.

Tablets were placed in a glass of water or orange or apple juice (100-200 Ml) and stir until a homogeneous suspension. The suspension is taken orally, after which its residues in the beaker was added small quantity of water or juice, stir and drink. It is not recommended to plant pills in carbonated drinks or milk, chew or swallow whole tablets.

Contraindications.

Hypersensitivity, galactose intolerance, severe lactase deficiency, glucose-galaktoznaya malyabsorbtsiya, pregnancy, lactation.

Carefully. Renal / hepatic impairment, hypercreatininemia above the age norm, increased activity of "liver" transaminases more than 5 time.

Side effect.

The incidence of side effects: Often (1/10 and more), often (more 1/100 less 1/10), sometimes (more 1/1000 less 1/100).

From the nervous system: often - headache; sometimes - dizziness, alarm, sleep disturbance.

From the senses: sometimes - early cataracts, makulopatija, hearing loss.

The respiratory system: sometimes - pain in the throat.

From the digestive system: often - diarrhea or constipation, dyspepsia, vomiting, nausea, gastralgia, flatulence, increased ALT, IS; sometimes - gastritis, hepatitis, cholelithiasis.

For the skin: often - a rash, itch; sometimes - pigmentation disorders.

From the urinary system: very often - hypercreatininemia, Parts - proteinuria.

Other: sometimes - hyperthermia, swelling, feeling tired.

Overdose

Symptoms: headache, nausea, vomiting, diarrhea.

Treatment: induction of vomiting or gastric lavage, simptomaticheskaya therapy.

Drug Interactions

Not to be combined with Al3 -containing antacids, PM, form complexes with iron ions.

Cautions.

Therapy should be held by a physician, with experience in the treatment of chronic iron overload posttransfusion.

It is recommended to determine the serum creatinine 2 times before treatment and monthly during treatment.

Adult patients the daily dose can be reduced by 10 mg / kg, if for two consecutive visits made more than nonprogressive gipekreatininemiya 50% compared to the average pre-treatment, and it could not be linked with other. causes. In children, the dose can be reduced by 10 mg / kg, if for two consecutive visits plasma creatinine greater than the upper limit of age norm. If there is a progressive increase in creatinine in excess of the upper limit of normal, drug therapy should be discontinued. The decision to resume therapy taken based on the specific clinical situation.

Monthly is recommended to control the activity of "liver" transaminases. With progressive increase in the activity of "liver" transaminases, not associated with any other. causes, therapy should be interrupted. After establishing the causes of changes or after normalization, You can consider resuming therapy.

With the development of rash of mild or moderate treatment should be continued without dose adjustment. With the development of more severe rash is necessary to interrupt treatment.

Before and during treatment with recommended regular monitoring of hearing acuity and ophthalmological research spending (ophthalmoscopy including fundus). In the case of hearing or visual impairment are recommended to consider the reduction of the dose or termination of therapy.

Month should determine the level of serum ferritin. Treatment should be discontinued, if the concentration of serum ferritin less 500 ug / l.

The children each 12 months is recommended to control weight and height.