Upritio 200mg Novartis treatment for heart failure (4 blisters x 7 tablets)

Cardiovascular supplementary efficiency and kidney effects on uproio in patients with heart failure are caused by sacubitrilat that increases the concentration of peptides that are decomposed by Neprilysin such as sodium peptides (NP) and inhibit effects and adverse effects of Angiotensin II by valsartan.

The NP shows the impact through the activity of the receptor of Guanylyl Cyclase mounted on the membrane, resulting in an increase in the concentration of guanosin monophosphate secondary communication ring (CGMP) thus the impact of vasodilation, increasing sodium and diuretic excretion, increasing glomerular filtration speed and giving blood flow through the kidneys, inhibiting the release of Renin and Aldosteron, reducing sympathetic and anti -fibrosis.

Prolonged activation of the renin-anodeensin-aldosteron system leads to vascular contractions, keeping salt water in the kidneys, triggering the growth and multiplication of the cell, causing adaptive restructuring. In addition, Valsartan inhibits the harmful effects on the heart and kidneys of Angiotensin II by inhibiting the AT1 receptor selection, while inhibiting the release of Aldosteron depends on Angiotensin II.

pharmacokinetic

absorption

After drinking, Sacubitril is converted into Sacubitrilat active. Sacubitril, Sacubitrilat and Valsartan reached the peak concentration in plasma after 0.5 hours, 2 hours and 1.5 hours respectively.

Absolutely organized oral Sacubitril and Valsartan are estimated at ≥ 60% and 23% respectively. When using the dose mode 2 times/day, Sacubitril, Sacubitrilat and Valsartan concentrations reach a stable state within 3 days. Food can reduce the levels of valsartan during circulation but do not reduce clinical treatment effects.

Distribution

Moderio is strongly linked to plasma proteins (94% - 97%). Sacubitrilate is less through the bloody barrier (0.28%). Uprenio has an apparent distribution of oscillation in the range of 75 - 103 l.

Metabolism

Sacubitril is easy to convert to sacubitrilat by the esters and sacubitrilat less metabolized. Only about 20% of Valsartan dose is metabolized. Sacubitril and Valsartan are less transformed through CYP450 intermediaries.

Elimination

After drinking, 52 - 68% Sacubitril (mainly Sacubitrilat), about 13% Valsartan and its metabolites are eliminated in urine. While 37 - 48% Sacubitril (mainly Sacubitrilat), 86% Valsartan and its metabolites are eliminated through feces.

Sacubitril, Sacubitrilat and Valsartan have an average selling time of about 1.43 hours; 11.48 hours and 9.90 hours.

When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Dual blockade Renin - Angiotensin - Aldosteron (RAAS)

Do not simultaneously use the uprio with enzyme inhibitors due to the risk of angioedema. Do not start using Uprerio within 36 hours after taking the end dose of enzyme inhibitors and vice versa, if stopped taking uprio, treated with enzyme inhibitors should not start within 36 hours after the last dose of the uproio.

Be cautious when using the uproio simultaneously with the direct inhibitors of renin (like Aliskiren). Do not simultaneously use the uprio with Aliskiren for patients with diabetes Type II.

Unserted with uproio with angiotensin receptor inhibitors due to the angiotensin II receptor blocker of the UPERIO.

Hypotension

should only start treatment when the patient's systolic blood pressure is ≥ 100 mmHg. Patients with systolic blood pressure

Uproio can cause symptomatic hypotension, especially patients ≥ 65 years old, have kidney disease or have low systolic blood pressure (

If hypotension occurs, temporarily reduces or stops treatment, and considers the dosage of diuretics, antihypertensive drugs and treats other causes of hypotension (such as reducing blood volume due to diuretics, low -salt diet, diarrhea or vomiting).

Need to adjust the deficiency of sodium and/or decrease the volume before starting to use the uprio, but be careful not to cause the volume overload.

Renal function impairment

regularly monitor kidney function. The severity of the kidney failure, the higher the likelihood of hypotension. Uprenio can reduce renal function and this risk increases when dehydration or simultaneous use of nonsteroidal anti -inflammatory drugs (NSAID). Consider reducing the dose in patients with impaired renal function of clinical significance.

Hemorrhage

Do not start and consider stopping treatment if the serum potassium level is> 5.4 mmol/l because the uprio can cause hyperkalemia (sometimes there is also hypotension). Monitoring serum potassium regularly, especially in patients with risk factors such as renal failure, diabetes or hypoglycemia, a diet high in potassium or taking mineralocorticoid antagonists.

If patients with clinical hyperkalemia are clinically significant, the dose should be adjusted simultaneously or temporarily reduced the dose or stop taking the drug.

Tharma

If the patient appears angiography when taking the drug, it should stop using the uprio immediately, monitor the condition, treat it until the symptoms are out of symptoms and do not reuse the uprio. If the angioedema appears to the face and lips, the angioedema will recover on its own without treatment, although it is possible to use antihistamines to reduce symptoms.

Thiche related to the subject can be fatal. If the angioedema in the tongue, the bar, the larynx is the cause of obstruction of the airway, it is necessary to implement appropriate treatments such as adrenalin injection 1: 1000 and/or measures to ensure ventilation.

Patients with renal artery stenosis

Uproio can increase blood urea and serum creatinine levels in patients with kidney stenosis on both sides or one side, so be careful when taking the drug for this object and regularly monitor kidney function.

Patients with heart failure IV according to NYHA

Be cautious when indicating the uprio for patients with NYHA level IV due to limited clinical experience.

Sodium type B (BNP) peptid

BNP is not a suitable biological indicator to monitor heart failure in patients using uprio because it is a substrate of Neprilysin.

Patients with liver failure

Clinical experience is limited in average liver failure patients (Classification of Child-Pough B) or AST/ALT> 2 ULN value. The concentration of medication in the blood may increase in this object, so the safety of the dose has not been authenticated.

The ability to drive and operate machinery

uprio can cause dizziness and fatigue, so patients are taking care of the drug when driving and operating machinery.

Pregnancy

There was a report on drug damage to the development of the fetus (such as natural miscarriage, amniotic fluid and kidney dysfunction in infants) when pregnant mothers use Valsartan. Patients who are using Uprerio should stop the drug immediately after detection of pregnancy and immediately notify the doctor.

Breastfeeding period

It is unknown whether the uprio is excreted in breast milk or not. Uproio should not be used for women who are breastfeeding due to the risk of harmful reactions for babies and young children. Consider stopping breastfeeding or stopping using uprio during breastfeeding, taking into account the importance of the Mother.

Drug interaction

Contraindicated interaction

Angiotesin (ACE) transferred enzyme inhibitors: Contraindications to use simultaneously with uprio with enzyme inhibitors due to increased risk of angioedema.

Aliskiren: Contrain to use simultaneously for patients with type II diabetes.

Interactive drugs recommend not to use coordination

Do not simultaneously use the uprio with Angiotensin II receptor blockers (ARB) due to the Angiotensin II receptor blocker of the uprio.

Avoid simultaneously with Aliskiren in patients with renal failure (EGFR estimated glomerular filtration speed

Interactions should consider when coordinating

Statin: According to in vitro, Sacubitril inhibits OatP1B1 and OatP1B3 transport protein protein, increases the plasma concentration of the statin - the substrate of these proteins. Simultaneous use with the Upreno doubled atorvastatin's CMAX concentration and the metabolites of the drug and increased 1.3 times the area under the AUC curve. Precautions when using simultaneously uprio and statin. However, there is no clinical interaction between the drug and the drug observed when used simultaneously simvastatin and uprio.

Inhibition PDE5 (including Sildenafil): Increased risk of hypotension is stronger than using alone each drug.

Potassium: Concomitant use with potassium diuretics (triamteren, amilorid), Mineralocorticoid receptor antagonists (spironolacton, eplerenon), potassium or potassium -containing salt can increase potassium levels and serum creatinine levels. Note to monitor serum potassium concentration if used simultaneously with these drugs.

Non -steroid anti -inflammatory drugs (NSAID) including cyclooxygenase inhibitors - 2: Increasing risk of bad kidney function in elderly patients, reduced weekly volume or impaired renal function.

Lithi: can cause increased serum lithium concentration and lead to toxicity, especially if combined with a diuretics.

Furosemide: Reduce CMAX and AUC of Furosemide as well as reduce sodium excretion through urine when used in combination.

Nitrate such as nitroglycerine: There is no drug interaction with drugs between uprio and nitroglycerine intravenously associated with hypotension. Simultaneous use of nitroglycerin and uproio is associated with the difference in the treatment of 5 BPMs of the heart rate compared to nitroglycerine, similar in nitrate under the tongue, taken or through the skin. In general, do not need to adjust the dose.

Oatp and MRP2 transport substances: The metabolites with the activity of sacubitril (sacubitrilat) and Valsartan are OatP1B1, OATP1B3 and OAT3; Valsartan is also MRP2. Therefore, simultaneous use of uproio with OatP1B1 inhibitors, OATP1B3, OAT3 (such as Rifampin, Cyclosprin) or MRP2 (such as Ritonavir) can increase Sacubitrilate or Valsartan levels in the circulation. Be careful when starting or stopping treatment with these drugs.

Metformin: Uprenio also reduces cmax and auc of metfomin when used simultaneously.