Камирен® HL

General characteristics. Structure:

Active ingredient: 4,85 mg of a doksazozin of a mezilat that is equivalent to 4,0 mg of a doksazozin.

Excipients: gipromelloza, calcium hydrophosphate anhydrous, lactoses monohydrate, magnesium stearate.

The drug rendering hypolipidemic, hypotensive, spasmolytic, vasodilating action.

Pharmacological properties:

Pharmacodynamics. Doksazozin is the selection blocker of alfa1-adrenoceptors. Interferes with reduction of smooth muscles of walls of peripheral vessels, reduces the general peripheric vascular resistance (GPVR), reduces the arterial pressure (AP).

Doksazozin has the anti-hypertensive effect which is not depending on age and position of a body of the patient.

Reduces before - and an afterload on a myocardium. After single use inside decrease in the ABP develops gradually, the maximum decrease is observed in 2-6 h, the anti-hypertensive effect remains during 24 h.

Contributes to normalization of a ratio of lipoproteins of the high density (LPVP) and the general cholesterol, reduces total concentration of triglycerides and cholesterol. 

It is effective at arterial hypertension, including followed by metabolic disturbances (obesity, a dislipidemiya, decrease in tolerance to glucose). At prolonged use regression of a hypertrophy of the left ventricle (LV), suppression of aggregation of thrombocytes, increase in activity in fabrics of the activator of plasminogen (plasminogen) and decrease in formation of collagen in walls of arteries is noted.

In response to use of the first dose development of orthostatic hypotension is characteristic. Use of a doksozazin for patients with the normal ABP is not followed by his decrease.

At patients with a benign hyperplasia of a prostate use of a doksazozin leads to improvement of urodynamic indicators and reduction of symptoms of a disease. The effect is connected with the selection blockade of alfa1-adrenoceptors of a subtype A (70% of all subtypes presented in a prostate) which are localized in a muscular stroma, the prostate capsule, a neck of a bladder and in proximal department of an urethra that reduces a muscle tone of a prostate and facilitates an urination. Renders effect at 66-71% of patients, the beginning of therapeutic effect - in 1-2 weeks of treatment.

Pharmacokinetics. The pharmacokinetics of a doksazozin of the prolonged action differs from a doksazozin with usual release. The drug Kamiren® HL is intended for the controlled release of a doksazozin for 24 h. Its relative bioavailability in comparison with doksazoziny usual release makes 54%.

The maximum concentration (Cmax) in plasma of 10,1±5,6 ng/ml is defined by 8,0±3,7 h. Communication with proteins of a blood plasma - about 98%.

Influence of food. Cmax and the area under a curve "concentration time" (AUC) of a doksazozin on average for 32% and 18% are higher after meal, in comparison with reception on an empty stomach. For prevention of sharp changes of concentration of a doksazozin in a blood plasma drug should be accepted during a breakfast.

Influence of time of a passage on intestines. Much the shortened drug passage time (e.g., a syndrome of short intestines) can influence pharmacokinetics of a doksazozin, reducing its concentration in a blood plasma. On the other hand increase in time of a passage on intestines (e.g., a chronic lock) can increase exposure of a doksazozin that leads to increase in risk of development of undesirable reactions.

Metabolism. It is metabolized in a liver. The researches in vitro demonstrate that the main way of elimination of drug occurs at the expense of CYP3A4 isoenzyme. In much smaller degree participation of isoenzymes of CYP2D6 and CYP2C19 is possible.

Removal. Doksazozin is brought through intestines, 5% - in not changed look are preferential in the form of metabolites (to 65%); through kidneys about 10% are removed. Elimination half-life about 15-19 h.

Influence of age. In an equilibrium condition of Cmax and AUC at elderly patients 65 years on average 27% higher and 34%, respectively, in comparison with young people are more senior.

Abnormal liver function. Use of a doksazozin for patients with a liver failure of easy severity (A class A on classification of Chayld-Pyyu) increases exposure of drug in comparison with patients without liver failure by 40%.

Indications to use:

- A benign hyperplasia of a prostate, both in the presence of arterial hypertension, and at the normal ABP.
-  Arterial hypertension (as a part of a combination therapy).

Route of administration and doses:

Inside, entirely, without chewing, washing down with a small amount of liquid, during a breakfast. If administration of drug of Kamiren® of HL is missed, in addition passed dose is not accepted and continue use of drug according to the established scheme.

Arterial hypertension. The recommended initial dose – 1 tablet (4 mg) of 1 times a day. After reception of the first dose the patient has to be in a bed during 6-8 h. It is required in communication that the development of a phenomenon of "the first dose" which is especially expressed against the background of the previous use of diuretics is probable. The maximum therapeutic effect is reached in 4 weeks of therapy. If after 4 weeks of therapy the effect is insufficient and the patient well transfers the drug Kamiren® HL, its dose can be increased. The maximum daily dose – 2 tablets (8 mg) of 1 times a day.

Benign hyperplasia of a prostate. The recommended dose – 1 tablet (4 mg) of 1 times a day. The maximum daily dose – 2 tablets (8 mg) of 1 times a day.

Elderly patients: dose adjustment is not required.

Renal failure: dose adjustment is not required.

Features of use:

Extra care should be observed at use of the drug Kamiren® HL for patients with an abnormal liver function, especially when at the same time use the drugs capable to change hepatic metabolism (for example, ethanol, phenylbutazone, Cimetidinum). In cases of change of "hepatic" transaminases the drug Kamiren® HL should be cancelled as soon as possible. For the purpose of prevention of orthostatic reactions patients have to avoid unexpected and sharp change of position of a body (transition from situation "lying" in a standing position).

It is necessary to be careful at simultaneous use of inhibitors of phosphodiesterase-5 and the drug Kamiren® HL since decrease in the ABP is possible. It is necessary to observe a 6-hour interval between use of inhibitors of phosphodiesterase-5 and use the drug Kamiren® HL (for reduction of risk of decrease in the ABP treatment is begun with use of inhibitors of phosphodiesterase-5).

At surgical interventions concerning a cataract against the background of use of the drug Kamiren® HL development of a syndrome of intraoperative instability of an iris of the eye of an eye is possible that needs to be considered when carrying out preoperative training of the patient and carrying out surgical intervention.

Alcohol intake is capable to strengthen side effect of the drug Kamiren® HL.

The effect of the "first" dose of the drug Kamiren® HL is especially expressed against the background of the previous therapy by diuretics and a diet with restriction of consumption of table salt.

Before therapy it is necessary to exclude a prostate cancer.

In researches доксазозин had no teratogenic and embriotoksichesky effect on animals. Use of the drug Kamiren® HL during pregnancy is possible only when the advantage for mother exceeds potential risk for the fruit/child. There are no data on penetration of a doksazozin into breast milk therefore in the period of a lactation, in need of use of the drug Kamiren® HL, breastfeeding should be stopped.

During treatment it is necessary to be careful at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of side effects of the World Health Organization (WHO):
very often  more than 1/10
often            from more than 1/100 to less than 1/10
infrequently        from more than 1/1000 to less than 1/100
seldom            from more than 1/10000 to less than 1/1000
very seldom  more than 1/10000

From cardiovascular system: often: the expressed decrease in the ABP, a heart consciousness, tachycardia; infrequently: stenocardia, myocardial infarction; very seldom: bradycardia, disturbance of a cordial rhythm, "inflows" of blood to face skin, peripheral hypostases.

From a nervous system: often: sleep disorder, dizziness, headache; infrequently: stroke, hypesthesias, faint, tremor, agitation, depression, uneasiness, nervousness, dysphonia, memory impairment, spasms; very seldom: paresthesias, postural dizziness.

From sense bodys: often: accommodation disturbance, photophobia, disturbance of a slezootdeleniye, disturbance of flavoring feelings; infrequently: a ring in ears; seldom: conjunctivitis; very seldom: illegibility of visual perception, miosis.

From the alimentary system: often: abdominal pain, dyspepsia, dryness of a mucous membrane of an oral cavity; infrequently: lock, abdominal distention, vomiting, diarrhea, increase in appetite, anorexia; very seldom: hepatitis, cholestatic jaundice.

From respiratory system: often: bronchitis, cough, short wind, rhinitis, xeromycteria; infrequently: nasal bleeding; very seldom: bronchospasm.

From a musculoskeletal system: often: dorsodynia, mialgiya; not often: arthralgia; seldom: spasms, weakness of muscles.

From integuments: often: skin itch; infrequently: skin rash; very seldom: small tortoiseshell, alopecia.

From urinogenital system: often: cystitis, urine incontience; infrequently: dysuria, hamaturia, impotence; seldom: polyuria; very seldom: frustration of an urination, nocturia, gynecomastia, priapism, retrograde ejaculation.

From a metabolism: infrequently: aggravation of a course of gout.

From system of a hemopoiesis: very seldom: Werlhof's disease.

Laboratory indicators: infrequently: hypopotassemia, increase in activity of "hepatic" transaminases; seldom: hypoglycemia, leukopenia, thrombocytopenia; very seldom: erythrocytopenia, uraemia, kreatininemiya.

General reactions: often: adynamy, thorax pain; infrequently: Quincke's disease of the person, decrease in body weight; very seldom: allergic reactions, increased fatigue.

Interaction with other medicines:

Doksazozin strengthens anti-hypertensive action of other antihypertensives (at simultaneous use with them dose adjustment of antihypertensives is required). 

Adverse interaction at simultaneous use of a doksazozin and thiazide diuretics, furosemide, beta adrenoblockers, blockers of "slow" calcium channels, inhibitors of an angiotensin-converting enzyme (APF), antibacterial agents, hypoglycemic means for intake, indirect anticoagulants and uricosuric means is noted.

Doksazozin does not influence extent of linkng with proteins of a blood plasma of digoxin, Phenytoinum, indometacin.

At simultaneous use with inductors of microsomal enzymes of a liver increase in efficiency of a doksazozin, with inhibitors - decrease is possible.

Cimetidinum increases AUC of a doksazozin.

Non-steroidal anti-inflammatory drugs (NPVP), especially indometacin, estrogen (liquid delay) and sympathomimetic means can reduce anti-hypertensive action of a doksazozin.

Eliminating alpha адреномиметические effects of Epinephrinum, use of a doksazozin can lead to development of tachycardia and decrease in the ABP.

Simultaneous use of a doksazozin with phosphodiesterase-5 inhibitors (including sildenafit, tadalafit, vardenafit) can lead to decrease in the ABP.

Contraindications:

Hypersensitivity to a doksazozin, to any other of components of drug or to other derivatives of quinazoline; a benign hyperplasia of a prostate with the accompanying disturbance of outflow of urine from upper parts of urinary tract, persistent infections of uric ways, stones in a bladder; lactose intolerance, deficit of lactase or syndrome of glyukozo-galaktozny malabsorption; intestinal impassability, impassability of a gullet; the expressed liver failure (A class C on classification of Chayld-Pyyu); the breastfeeding period, the expressed liver failure, age up to 18 years (efficiency and safety are not established).

With care. An aortal and/or mitral stenosis, right-hand heart failure owing to an embolism of a pulmonary artery or an exudative pericardis, left ventricular heart failure with low filling pressure, simultaneous use of inhibitors of phosphodiesterase-5 (sildenafit, vardenafit, tadalafit), a syndrome of intraoperative instability of an iris of the eye of an eye, a slight and moderate liver failure (A class A and B on classification of Chayld-Pyyu), tendency to arterial hypotension (orthostatic disturbances of regulation of a krovobrashcheniye), pregnancy.

Overdose:

Symptoms: the expressed decrease in the ABP, a headache, a loss of consciousness, an asthma, a heart consciousness, tachycardia, disturbances of a heart rhythm, nausea, vomiting, are possible a hypoglycemia and a hypopotassemia.

Treatment: gastric lavage, reception of absorbent carbon; the patient needs to be transferred to situation "lying" on spin and to raise legs. At the expressed decrease in the ABP to hold events for completion of the volume of the circulating blood (VCB), if necessary to apply vazopressor.

The hemodialysis is inefficient since it доксазозин almost completely contacts proteins of a blood plasma.

Storage conditions:

To store at a temperature not above 30 °C in the places not available to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated, 4 mg. On 10 tablets in the blister from the combined material polyamide / an aluminum foil / PVH-the aluminum foil covered from two parties with a heat-resistant varnish (Coldforming OPA/Al/PVC-Al). 1, 3, 9 blisters place in a pack cardboard together with the application instruction.