Doxazosin-FPO, tablets 4 mg 30 pcs

Pharmaceutical group:

alpha1-adrenoblocker

Pharmacodynamics:

Doxazosin is a selective competitive blocker of postsynaptic alpha1-adrenoreceptors (affinity for alpha1-adrenoreceptors is 600 times higher than for alpha2-adrenoreceptors), reduces total peripheral vascular resistance (PPR), prevents catecholamine-induced vasoconstriction, which ultimately leads to lower blood pressure (BP) without development of reflex tachycardia.

Limits the pre- and post-load on the heart. After a single dose, the decrease in BP develops gradually, the maximum decrease is observed in 2-6 hours and persists for 24 hours.

After a single dose of the drug, the maximum hypotensive effect is observed within 2 to 6 hours, and the overall hypotensive effect is maintained for 24 hours. During treatment with doxazosin in patients with arterial hypertension (AH) there is no difference in BP values in “standing” and “lying” position.

It is effective in AH, including when accompanied by metabolic disorders (obesity, decreased glucose tolerance).

Limits the risk of coronary heart disease (CHD). Administration of the drug in patients with normal BP is not accompanied by a decrease in BP. With long-term use of doxazosin, patients develop tolerance.

Long-term treatment with doxazosin shows regression of left ventricular (LV) hypertrophy, suppression of platelet aggregation and increased content of active plasminogen in tissues.

Due to the fact that doxazosin blocks alpha1-adrenoreceptors located in the stroma and capsule of the prostate and in the bladder neck, there is a decrease of resistance and pressure in the urethra, reduction of internal sphincter resistance. Therefore administration of doxazosin to patients with symptoms of benign prostatic hyperplasia (BPH) results in significant improvement of urodynamic parameters and reduction of manifestation of the disease symptoms.

It has an effect in 66-71% of patients; the beginning of the effect is after 1-2 weeks of treatment and maximum effect is reached after 14 weeks; the effect remains long time.

Pharmacokinetics:

After oral administration at therapeutic doses, doxazosin is well absorbed, absorption is 80-90% (simultaneous food intake slows absorption by 1 hour), time to reach maximum plasma concentration (TCmax) is 3 hours, with TCmax prolonged to 5 hours with evening administration.

The bioavailability is 60-70%. Blood plasma protein binding is about 98%. Excretion from blood plasma occurs in 2 phases with final half-life (T½) – 19-22 hours, which allows to prescribe the drug once a day.

It is intensively metabolized in the liver by o-demethylation and hydroxylation. In patients with impaired hepatic function and when taking drugs which can change “hepatic” metabolism the process of biotransformation of the drug may be impaired. Main excretion is through intestine (63-65% as metabolites and about 5% – unchanged).

You can excrete about 10% by kidneys. Study of doxazosin pharmacokinetics in elderly patients and patients with kidney disease showed no significant pharmacokinetic differences.

Indications

Active ingredient

Composition

1 tablet contains:

the active ingredient:

doxazosin mesylate 1.22 mg/2.44 mg/ 4.88 mg (in terms of doxazosin

1 mg/2 mg/4 mg);

auxiliary substances:

Lactose monohydrate 80.18 mg/

90.16 mg/180.32 mg;

calcium phosphate 17.0 mg/35.0 mg/70.0 mg;

povidone K30 0.4 mg/0.6 mg/1.2 mg;

Sodium lauryl sulfate 0.2 mg/0.3 mg/ 0.6 mg;

calcium stearate 0.5 mg/1.0 mg/ 2.0 mg;

talc

0.5 mg/0.5 mg/1.0 mg

How to take, the dosage

Once daily (morning or evening) by mouth, regardless of meals, without chewing and with plenty of water.

Patients with hepatic impairment require smaller doses due to slower metabolism of the drug.

If a patient forgets to take the drug at the usual time, he should take the appropriate dose of the drug as soon as possible. If it is time for the next dose, only this dose (do not double the dose) should be taken. It is important to take the medication regularly. If the patient has not taken the medication for several days, the new therapy should be started with the lowest dose.

PAD: The initial dose is 1 mg of doxazosin per day. The patient should take the first dose in the evening before going to bed. Depending on urodynamic parameters and the presence of symptoms of BPH, the dose may be gradually increased at 1-2 week intervals to 2 mg, 4 mg and 8 mg per day. The recommended maintenance dose is 2 to 4 mg per day. The maximum daily dose is 8 mg.

After achieving a sustained therapeutic effect, the dose is usually reduced (the average therapeutic dose for maintenance therapy is usually 2-4 mg daily).

AH: The initial dose of doxazosin is 1 mg daily before bedtime. After the first dose, the patient should be in bed for 6-8 hours. This is required due to the possibility of development of “first dose” phenomenon, especially pronounced against the background of previous diuretics administration. If the therapeutic effect of the drug is insufficient, the daily dose may be increased to 2 mg after 1-2 weeks.

The dose may be increased by 2 mg every 1-2 weeks thereafter. In the vast majority of patients the optimal therapeutic effect is achieved at a dose of 8 mg per day. The maximum daily dose is 16 mg.

Interaction

Doxazosin enhances the antihypertensive effect of hypotensive agents (when used in combination with them a dose adjustment is required).

No adverse interaction has been noted with concomitant use of doxazosin and thiazide diuretics, furosemide, beta-adrenoblockers, “slow” calcium channel blockers, angiotensin-converting enzyme inhibitors, antibacterial agents, hypoglycemic agents for oral administration, indirect anticoagulants and uricosuric agents.

The drug has no effect on the degree of binding to plasma proteins of digoxin, phenytoin.

When used concomitantly with inducers of enzymes of microsomal oxidation in the liver (ethanol, barbiturates, phenylbutazone, tricyclic antidepressants) the effectiveness of doxazosin may increase, with inhibitors (cimetidine) – decrease.

Non-steroidal anti-inflammatory drugs (NSAIDs), especially indomethacin, estrogens (fluid retention) and sympathomimetics may decrease the hypotensive effects of doxazosin.

By eliminating the alpha-adrenergic stimulating effects of epinephrine, may lead to tachycardia and arterial hypotension.

Concomitant use with selective phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil) may lead to arterial hypotension.

Special Instructions

Special caution should be exercised when using Doxazosin in patients with hepatic dysfunction, especially in cases when concomitant use of drugs that may alter hepatic metabolism (e.g., ethanol, barbiturates, phenylbutazone, tricyclic antidepressants, cimetidine). In cases of deterioration of liver function parameters the drug should be immediately discontinued.

In order to prevent orthostatic reactions, patients should avoid sudden and abrupt changes of body position (transition from “lying” to “standing”).

Phosphodiesterase-5 inhibitors and doxazosin should be used with caution during concomitant administration because arterial hypotension may occur. To decrease the risk of arterial hypotension (including orthostatic), initiate treatment with phosphodiesterase-5 inhibitors only if the patient has adapted to doxazosin therapy, moreover, a 6-hour interval between the intake of drugs from doxazosin administration should be observed.

In surgical procedures for cataract with this drug intraoperative iris instability syndrome (narrow pupil syndrome) may develop, which should be considered by the surgeon for preoperative preparation of the patient and during the surgery.

Alcohol intake may increase adverse reactions to doxazosin.

The “first dose” effect of the drug is particularly pronounced with prior diuretic therapy and a sodium restricted diet.

Before starting therapy, prostate cancer must be excluded.

Influence on driving and other machinery

When taking the drug Doxazosin, caution should be exercised when driving vehicles or performing work requiring increased concentration and speed of psychomotor reactions.

Contraindications

Hypersensitivity to doxazosin and other quinazoline derivatives (prazosin, terazosin) or other components of the drug;

Persons with a tendency to orthostatic hypotension;

AH (for patients with benign prostatic hyperplasia);

Patients with BPH and associated upper urinary tract outflow disorders, chronic urinary tract infections, bladder stones;

Lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

Lactation period;

Age under 18 years (effectiveness and safety not established);

As monotherapy in patients with either bladder overflow or anuria with or without progressive renal failure.

C Caution: Pulmonary edema due to aortic or mitral stenosis;

Right-sided heart failure due to pulmonary embolism or exudative pericarditis;

Left ventricular heart failure with low filling pressure;

Concurrent use of phosphodiesterase-5 inhibitors (sildenafil, vardenafil, trandalafil);

Intraoperative iris instability syndrome (narrow pupil syndrome);

Liver function impairment.

Side effects

The frequency of adverse reactions when using Doxazosin is given below according to generally accepted classification:

Very common (≥1/10); common (≥1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000).

Cardiovascular system: frequently – AH (including orthostatic), palpitations, tachycardia; infrequently – angina pectoris, myocardial infarction; very rarely – bradycardia, arrhythmia, “flushes” of blood to the skin, peripheral edema.

The central and peripheral nervous system: frequently – somnolence, dizziness, headache; infrequently – stroke, hypoesthesia, syncope, tremor, agitation, depression, anxiety, insomnia, nervousness; very rarely – paresthesia, postural dizziness.

Senses: frequently – vertigo; infrequently – tinnitus; very rarely – blurred vision, syndrome of narrow pupils.

The digestive system: frequently – abdominal pain, dyspepsia, dry mouth; infrequently – constipation, bloating, vomiting, diarrhea, increased activity of “liver” enzymes, loss of appetite, anorexia; very rarely – hepatitis, cholestasis, jaundice.

Respiratory system: often – bronchitis, cough, shortness of breath, rhinitis, dry nasal mucosa; infrequent – nasal bleeding; very rare – bronchospasm.

Hematopoietic disorders: leukopenia, thrombocytopenia.

Muscular system: often – back pain, myalgia; not often – arthralgia; rarely – cramps, muscle weakness.

The skin: often – itching; infrequent – skin rash; very rare – urticaria, allopecia, purpura.

Urogenital system: often cystitis, urinary incontinence; not often – dysuria, increased frequency of urination, hematuria, impotence, gout; rarely – polyuria; very rarely – increased diuresis, urinary disorders, nycturia, gynecomastia, priapism, retrograde ejaculation.

General reactions: frequent – asthenia, chest pain, malaise; infrequent – pain, facial swelling, weight loss; very rare – allergic reactions, fatigue.

Overdose

Symptoms: marked decrease in BP, sometimes accompanied by fainting.

Treatment: gastric lavage, administration of activated charcoal.

The patient should be placed on his back and his legs raised. In case of a pronounced decrease in BP, antishock measures are performed – circulating blood volume is replenished, if necessary, vasopressors are prescribed.

Hemodialysis is ineffective.

Similarities