SPIRIVA
Active material: Tiotropium bromide
When ATH: R03BB04
CCF: Bronchodilators – m-blocker holinoreceptorov
ICD-10 codes (testimony): J43, J44, J45
When CSF: 12.01.04
Manufacturer: BOEHRINGER Ingelheim International GmbH (Germany)
Pharmaceutical form, composition and packaging
Capsules with powder for inhalation hard gelatin, pale greenish blue, opaque; symbol of the company and “OF 01”, printed in black ink; contents of capsules – white powder.
| 1 caps. | |
| tiotropium | 18 g |
| equal tiotropium bromide monohydrate (= Tiotropium bromide) | 22.5 g |
Excipients: lactose monohydrate, 200 M; lactose monohydrate micronized.
Capsule: macrogol 3350 (PEG 3350), indigokarmin (E132), Titanium dioxide (E171), iron oxide yellow (E172).
10 PC. – blisters (1) Included inhaler HandiHaler® or without – packs cardboard.
10 PC. – blisters (3) Included inhaler HandiHaler® or without – packs cardboard.
10 PC. – blisters (6) Included inhaler HandiHaler® or without – packs cardboard.
Pharmacological action
Bronchodilators – m-cholinergic receptor blocker, long-acting.
It has the same affinity for the different subtypes of muscarinic receptors M1 to M5. As a result of inhibition of M3-receptors in airway smooth muscle relaxation occurs. Bronchodilatory effect depends on the dose and maintained for at least 24 no. A significant duration of action is associated, probably, with very slow release of an M3-receptors, compared to ipratropium bromide. When inhaled tiotropium bromide, as an anticholinergic agent N-quaternary structure, It has a local selective action, wherein at therapeutic doses do not cause systemic side effects of anticholinergic. Release of tiotropium bromide of an M2-receptors is faster, than an M3-receptors. High affinity receptors and slow release of the connection therewith determine the intensity and duration bronchodilatory effect in patients with COPD.
Bronchodilation following inhalation of tiotropium bromide is a consequence of the local, and not systemic action.
Clinical studies have shown, that through 30 minutes after a single dose of Spiriva® for 24 h significantly improves lung function (increase in FEV1 and FVC). Pharmacodynamic balance is achieved within 1 week, and pronounced bronchodilator effect was observed on Day 3. Spiriva® significantly increases the morning and evening peak expiratory flow stream, measured patients. Bronchodilator effect of Flomax®, estimated for the year, showed no symptoms of tolerance.
Spiriva® significantly reduces COPD exacerbations and increases the period before the first exacerbation compared to placebo. Significantly improves quality of life, that is observed during the treatment period. Spiriva® significantly reduces the number of hospital admissions, associated with acute exacerbation of COPD, and increases the time until the first hospitalization.
Pharmacokinetics
Tiotropium bromide – Quaternary ammonium compound, sparingly soluble in water.
Tiotropium bromide, has a linear pharmacokinetics in the therapeutic range after / in the dry powder inhaler and.
Absorption
When inhaled, the absolute bioavailability of tiotropium bromide is 19.5%, which indicates a high bioavailability of the drug faction, reaching the lungs. Cmax plasma levels achieved after 5 minutes after inhalation. Tiotropium bromide is poorly absorbed from the gastrointestinal tract. For this reason, eating does not affect the absorption of tiotropium. If ingestion of tiotropium bromide in the form of a solution was an absolute bioavailability 2-3%.
Distribution
Plasma protein binding – 72%. Vd – 32 l / kg. In equilibrium Cmax in blood plasma in patients with COPD is 17-19 pg / ml at 5 min after the inhalation of the powder in the dose 18 mcg and decreases rapidly. Css in plasma were 3-4 pg / ml.
Do not cross the BBB.
Metabolism
The extent of biotransformation is small. Tiotropium bromide is split up by the non-enzymatic alcohol and N-metilskopina ditienilglikolevoy acid, that do not bind to muscarinic receptors.
Metabolic disorder possible using inhibitors isoenzymes CYP2D6 and 3A4 (xinidina, ketoconazole, gestodene). Thus, 3A4 isoenzymes CYP2D6 and are included in drug metabolism. Tiotropium bromide even in sverhterapevticheskih concentrations does not inhibit cytochrome P450 1A1, 1A2, 2B6, 2C9, 2C19, 2D6, 2E1 or 3A4 in human liver microsomes.
Deduction
After inhalation terminal T1/2 is 5-6 days. The total clearance at / introduction of healthy young volunteers 880 ml / min, when individual variability 22%. Tiotropium bromide after the on / in the output, primarily, the urine in unchanged form – 74%. After inhalation powder renal excretion of 14%, the rest of the, not absorbed into the intestine, excreted in the feces. The renal clearance of tiotropium bromide exceeds QC, indicating that tubular secretion of the drug. After prolonged use of the drug 1 time / day in patients with COPD equilibrium state pharmacokinetic parameters is achieved through 2-3 of the week, wherein there is no further accumulation.
Pharmacokinetics in special clinical situations
In elderly patients, a decrease of tiotropium bromide renal clearance (326 ml / min in patients with COPD before 58 years, to 163 mL / min in patients with COPD over 70 years), due, apparently, reduction in renal function with age. After inhalation urinary excretion of tiotropium bromide is reduced to 14% (young healthy volunteers) to 7% (Patients with COPD), However, elderly patients with COPD there were no significant changes in plasma concentrations of, given between- and intraindividual variability (After inhalation powder increased AUC0-4 on 43%).
If the kidney function after inhalation and / in the introduction of enhanced drug concentration in blood plasma and reduced renal clearance. In mild renal dysfunction (CC 50-80 ml / min), often observed in elderly patients, increasing the concentration of tiotropium bromide plasma insignificantly (after the on / in the increase in AUC0-4 on 39%). COPD patients with moderate or severe degree of renal function reduction (CC < 50 ml / min) after / in the ipratropium bromide is observed a twofold increase in its concentration in blood plasma (82% increase in AUC0-4), compared with concentrations in blood plasma, determined after inhalation of dry powder.
Expected, that liver failure will not have a significant effect on the pharmacokinetics of tiotropium bromide, tk. the drug is mainly excreted in the urine and the formation of the pharmacologically active metabolite is not related to the participation of enzymes.
Testimony
- As maintenance therapy in patients with COPD, including chronic bronchitis and emphysema, (maintenance therapy for persistent dyspnea, and for the prevention of exacerbations).
Dosage regimen
Assign 1 caps. / day at the same time by inhalation using the inhaler HandiHaler.
The drug should not swallow. Spiriva® should not be used more often, than 1 time / day. Flomax Capsules® You should only be used with an inhaler HandiHaler.
Elderly patients should take the drug at the recommended doses.
At renal impairment Patients can use Flomax® at recommended doses. However, the appointment of Spiriva® in combination with other drugs, which are derived mainly kidneys, requires monitoring of patients. Patients with kidney failure moderate or severe (KK≤50 ml / min) should be closely monitored.
Patients with hepatic insufficiency may take the drug at the recommended doses.
How to use an inhaler HandiHaler®
The inhaler HandiHaler is designed specifically for use Flomax® and is not intended for receiving other medications.
The inhaler comprises: Dust Cap, mundştuk, ground, button piercing, central chamber.
Using the inhaler HandiHaler:
1. open the dust cap, pressing the piercing button completely, then release;
2. fully open the dust cap, lifting it up; then open the mouthpiece, lifting it up;
3. immediately prior to use to get Flomax capsule® from the blister and put it into the central chamber (irrelevant, which side the capsule is placed in the chamber);
4. tightly close the mouthpiece until it clicks, dust cap is left open;
5. HandiHaler holding mouthpiece up, press the piercing button once to the end and then release; thus, a hole, through which the drug is released from the capsule during inhalation;
6. fully exhale; never exhale into the mouthpiece.
7. take the HandiHaler to your mouth and tightly compressed lips around the mouthpiece; keeping your head up, inhale slowly and deeply, but at the same time with sufficient force, to hear the vibration of the capsule; to breathe to full fill light; then hold your breath as long as possible and remove the HandiHaler mouth; continue to breathe calmly; repeat procedure 6 and 7 for the complete emptying of the capsule.
8. followed by re-open the mouthpiece, get it and throw the used capsule. Close the mouthpiece and dust cap.
Cleaning the inhaler HandiHaler®
Clean the HandiHaler should be 1 once a month. To do this, open the mouthpiece and dust cap, then open the base unit, lifting the piercing button. Rinse thoroughly with warm water in the inhaler to completely remove the powder. HandiHaler should be wiped with a paper towel and open the mouthpiece, a base and a dust cap leave to air dry for 24 no. After cleaning this way the device is ready for subsequent use. If necessary, the outer surface of the die can be cleaned with a damp, but not wet tissue.
Vskrыtie blister
Separate the blister strip along the perforated line. Open the blister strip immediately before use so, that one capsule was fully visible. The capsule contains a small amount of powder, so it is not completely filled.
When, if the capsule was accidentally opened and exposed to air, it should not be used. Neither device, or in blister Capsules should not be exposed to high temperatures, sunlight.
Side effect
From the digestive system: small dry mouth, often disappear with continued treatment (≥ 1% and < 10%); oral candidiasis (≥ 0.1% and < 1%); constipation, hastroэzofahealnыy reflux (≥ 0.01% and < 1%); in a few cases – ileus (including paralytic ileus), dysphagia.
The respiratory system: disfonija, bronchospasm, cough and local irritation of the throat (≥ 0.1% and < 1%); nose bleed (≥ 0.01% and < 1%).
Cardio-vascular system: tachycardia, heartbeat (≥ 0.01% and < 1%); in a few cases – supraventricular tachycardia, atrial fibrillation.
CNS: dizziness (≥ 0.1% and < 1%).
From the urinary system: difficulty urinating and urinary retention in men with predisposing factors, urinary tract infections (≥ 0.01% and < 1%).
Allergic reactions: rash, hives, itch, hypersensitivity reactions, including immediate reactions (≥ 0.01% and < 1%); in a few cases – angioedema.
Other: in a few cases – blurred vision, increased intraocular pressure (≥ 0.01% and < 1%); glaucoma.
Most of the above adverse reactions may be associated with anticholinergic Spiriva®.
Contraindications
- I trimester of pregnancy;
- Childhood and adolescence up 18 years;
- Hypersensitivity to atropine or its derivatives (incl. to ipratropium and oxitropium);
- Hypersensitivity to the drug.
FROM caution use in patients with angle-closure glaucoma, prostatic hyperplasia, bladder outlet obstruction.
Pregnancy and lactation
The drug is contraindicated for use in the I trimester of pregnancy.
In II and III trimesters of pregnancy and lactation the drug should be administered only in cases, when the expected benefit of therapy to the mother outweighs the potential risk to the fetus or infant.
Cautions
The drug Flomax® not intended for the relief of acute episodes of bronchospasm.
After inhalation powder Flomax® may develop immediate hypersensitivity reactions.
The process of inhalation Flomax® (as well as other inhalants) can cause bronchospasm.
Patients with renal insufficiency (CC ≤ 50 ml / min) the appointment of Spiriva® It should be carefully monitored.
Patients should read the rules of use of the inhaler. Do not allow to enter the powder into the eyes. Eye pain or discomfort, blurred vision, visual halos in conjunction with eye redness, conjunctival congestion and corneal edema may indicate an acute attack of angle-closure glaucoma. With the development of any combination of these symptoms the patient should seek medical advice immediately. Application only drugs, causing cramps, It is not an effective treatment in a given case,.
One capsule contains 5.5 mg lactose monohydrate.
Use in Pediatrics
Do not use this drug in children and adolescents up to 18 years.
Effects on ability to drive vehicles and management mechanisms
Studies on the effect of the drug on the ability to drive vehicles and management mechanisms has not been. Cases of dizziness and blurred vision when applying the drug may have a negative impact on the ability of the above.
Overdose
Symptoms: when high doses are possible manifestations of anticholinergic action – dry mouth, accommodation disturbances, increase in heart rate.
After inhalation of a single dose of 282 mg in healthy volunteers revealed no systemic anticholinergic effects. After repeated administration once daily dose 141 mg in healthy volunteers was observed bilateral conjunctivitis combined with dry mouth, who disappeared with continued treatment. In the study, which examined the effects of tiotropium with repeated use in patients with COPD, receiving the maximum 36 micrograms of the drug more 4 weeks, Dry mouth was the only side effect.
Ostraya intoxication, associated with a casual reception inside capsules, unlikely because of the low bioavailability of the drug.
Drug Interactions
Perhaps the appointment of Spiriva® in combination with other drugs, Typically used for the treatment of COPD: simpatomimetikami, methylxanthine derivatives, oral and inhaled corticosteroids.
Limited information on the combined use of anticholinergic drugs is derived from two clinical trials: a one-time appointment 1 doses of ipratropium bromide on a background of continuous use Flomax® COPD patients (64 man) in healthy volunteers (20 man) It does not lead to a decrease in adverse reactions, change of life parameters and ECG. However, a permanent combined use of anticholinergic drugs and Flomax® It has not been investigated and, Consequently, not recommended.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or above 25 ° C; Do not freeze. Shelf life – 2 year.
After opening the blister for use 9 days.
HandiHaler Device can be used for 1 year.
