Adenuric tabs 80mg #28

Adenuric user manual

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Adenuric is an anti-gout drug.

Release form and composition

The drug is produced in the form of film-coated tablets: oblong, from pale yellow to yellow, on one side with embossed "80" or "120", depending on the dosage (14 pcs. In a blister strip, in a cardboard box 2, 4 or 6 packs / blisters and instructions for use of Adenuric).
1 film-coated tablet contains:
    active substance: febuxostat - 80 or 120 mg;
    additional components: hyprolose, lactose monohydrate, microcrystalline cellulose (Avicel PH101 and Avicel PH102), croscarmellose sodium, magnesium stearate, water colloidal silicon dioxide;
    film shell: Opadray II yellow 85F42129 [macrogol 3350, polyvinyl alcohol, talc, titanium dioxide (E171), dye yellow iron oxide (E172)].

Pharmacodynamics

Uric acid is the end product of purine metabolism in the human body, formed as a result of a cascade of reactions hypoxanthine → xanthine → uric acid.
Febuxostat, the active substance of the drug, a derivative of 2-arylthiazole, is a potent selective non-purine inhibitor of xanthine oxidase (the in vitro inhibition constant of this enzyme is less than 1 nM). Xanthine oxidase catalyzes two stages of purine metabolism: the oxidation of hypoxanthine to xanthine, and then xanthine to uric acid.
The decrease in serum uric acid levels in the blood is due to the selective suppression of xanthine oxidase (oxidized and reduced forms) by febuxostat. In therapeutic concentrations, the active substance does not inhibit enzymes such as OPRT (orotate phosphoribosyltransferase), PNP (purine nucleoside phosphorylase), HGFRT (hypoxanthine guanine phosphoribosyltransferase), guanine deaminase, or orotidine boxyl monophosphate dextrose.
The safety profile and clinical efficacy of febuxostat in the treatment of gout.
The safety and efficacy of febuxostat has been documented in three pivotal phase III clinical trials (FACT, APEX and CONFIRMS) in 4101 patients with gout and hyperuricemia. According to the results of these studies, Adenuric was more effective in lowering uric acid and maintaining serum uric acid levels when compared with allopurinol.
The 28-week APEX study included 1,072 patients. Patients received once a day: febuxostat in doses of 80, 120 or 240 mg; allopurinol at a dose of 300 mg (with an initial plasma creatinine level of ≤ 1.5 mg / dl) and at a dose of 100 mg (with an initial creatinine content of> 1.5 mg / dl and ≤ 2.0 mg / dl). Due to the use of febuxostat in doses of 120 mg and 80 mg once a day for 28 weeks, the number of patients whose serum uric acid content did not exceed 6 mg / dL (357 μmol / L) during the last 3 months was 65 and 48% accordingly, when using allopurinol - 22%.
760 patients participated in the double-blind, randomized, 52-week FACT trial. When taking febuxostat 1 time per day at doses of 120 mg and 80 mg during the entire study period, the proportion of persons whose serum uric acid level did not exceed 6 mg / dL (357 μmol / L) during the last 3 months was 62 and 53%, respectively, and when using allopurinol once a day at a dose of 300 mg - 21%. The use of febuxostat provided a rapid decrease in plasma uric acid levels over a long period of time. A decrease in the serum uric acid content in the blood of less than 6 mg / dL (357 μmol / L) was recorded already in the second week of use (FACT study), this level of concentration was maintained throughout therapy with febuxostat.
In conducting a randomized controlled 26-week study CONFIRMS, 2269 patients were involved, at least 65% had mild to moderate renal impairment, with creatinine clearance (CC) of 30–89 ml / min. Due to the use of febuxostat once a day at a dose of 80 mg and 40 mg, the number of patients whose plasma uric acid level was less than 6 mg / dL at the last visit to the doctor was 67 and 45%, respectively, for allopurinol at a daily dose of 300 mg. and 200 mg - 42%.
The open-label, multicenter, randomized, extended safety study EXCEL compared with allopurinol included 1,086 people who completed the FACT or APEX study. The target serum uric acid level (less than 6.0 mg / dL), which was achieved against the background of previous administration of febuxostat, did not change over time - in 91 and 93% of patients initially receiving febuxostat at doses of 80 mg and 120 mg, uric acid concentration was less than 6 mg / dL at 36 months of treatment. According to the results of three-year follow-up, there was a decrease in the incidence of gout attacks at 16-24 and 30-36 months, while more than 96% of patients did not need to treat gout attacks. In 46 and 38% of patients receiving the drug constantly 1 time per day, respectively, at a dose of 80 mg and 120 mg, by the last visit, there was a complete disappearance of initially palpable tophi.
A five-year, open-label, multicenter, extended safety study FOCUS (Phase II) enrolled 116 patients initially treated with febuxostat 80 mg once daily for 4 weeks. No dose adjustments were required to maintain serum uric acid levels below 6 mg / dL in 62% of patients, and dose adjustments were required to achieve the target level in 38% of patients. At the last visit, the proportion of patients with a serum uric acid concentration of less than 6 mg / dL was more than 80% for each dose of febuxostat studied.
In a prospective analysis in the CONFIRMS study, febuxostat was found to be significantly more effective in reducing serum uric acid to less than 6 mg / dL compared to allopurinol 300 mg and 200 mg in patients with gout and mild to moderate renal failure. ...
The safety profile and clinical efficacy of febuxostat in the treatment of tumor disintegration syndrome (TSS).
In a randomized, double-blind phase III trial (FLORENCE), the safety and efficacy of using febuxostat for prophylaxis and therapy of FRO was studied. In the study, febuxostat showed a more intense and rapid decrease in serum uric acid levels compared to allopurinol, while there was no negative effect on renal function. The study involved 346 patients with hematological malignancies, who underwent cytostatic therapy, and who had a medium / high degree of threat of FRO. Evaluation of the effectiveness of Adenuric in maintaining the level of uric acid in the blood serum and evaluation of its effect on renal function was carried out against the background of taking 1 time per day at a dose of 120 mg or using allopurinol in a daily dose of 200-600 mg. Patients participating in the study were required to be treated with allopurinol or were not able to be treated with rasburicase.
The study found that the mean area under the concentration-time curve (AUC) over 8 days was significantly lower with Adenuric than with allopurinol. 24 hours after starting the course of treatment with febuxostat and in all further measurements, there was a significantly lower mean serum uric acid level compared with the allopurinol group. There were no statistically significant differences in the effect of febuxostat and allopurinol on plasma creatinine in the blood. Also, statistically significant differences in the incidence of FRO with the use of febuxostat and allopurinol were not recorded either by clinical criteria or by the criteria of laboratory diagnostics.

Pharmacokinetics

The population analysis of the pharmacokinetics / pharmacodynamics of the drug contains data obtained in a study involving 211 patients with hyperuricemia and gout who used the drug once a day in a dose range of 40–240 mg. The recorded values ​​of the pharmacokinetic parameters of febuxostat corresponded to those in healthy volunteers, which allows the data from studies conducted with the participation of healthy volunteers to be considered representative of the population of patients with gout.
After oral administration, febuxostat is intensively and almost completely (not less than 84% of the administered dose) absorbed from the gastrointestinal tract (GIT). With repeated use of a dose of Adenuric 80 mg or with a single dose of 120 mg in combination with food rich in fats, its maximum plasma concentration (Cmax) decreased by 49 and 38%, and AUC decreased by 18 and 16%, respectively. However, these reactions did not affect the decrease in serum uric acid levels in the blood (against the background of repeated use of febuxostat at a dose of 80 mg) and the clinical efficacy of the drug. Adenuric in this way can be used regardless of the time of the meal.
After oral administration, Cmax is observed after 1-1.5 hours and is 2.8-3.2 mcg / ml with a single dose of Adenuric 80 mg, and 5-5.3 mcg / ml at a dose of 120 mg. The absolute bioavailability of the active substance in tablet form has not been studied. In the case of a course of oral administration of the drug in the dose range of 10–240 mg 1 time per day, cumulation was not observed.
With a single / multiple oral administration of Adenuric in healthy volunteers with increasing doses in the range from 10 to 120 mg, Cmax and AUC of the funds increase linearly, and in the dose range from 120 to 300 mg, an increase in AUC is observed to a greater extent than proportionate to the dose.
The apparent volume of distribution (Vd) at steady state after 10–300 mg of febuxostat can vary from 29 to 75 liters. The drug binds to plasma proteins (mostly albumin) by 99.2%. In this case, the degree of binding in the case of increasing the dose from 80 to 120 mg does not change. The connection of active metabolites with plasma proteins is 82–91%.
The metabolic transformation of febuxostat is carried out by conjugation with the participation of uridine diphosphate glucuronyl transferase (UDPGT) and oxidation by enzymes of the cytochrome P450 system (CYP). Four pharmacologically active hydroxyl metabolites of febuxostat have been identified, three of which are detected in human plasma. In the process of in vitro studies on liver microsomes, it was demonstrated that oxidized metabolites are formed mainly under the influence of isoenzymes CYP2C9, CYP2C8, CYP1A2 or CYP1A1, while febuxostat glucuronide is formed mainly due to the action of isoenzymes UGT1A9, UGT1A1 and UGT1A8.
The active substance and its metabolites are excreted from the body through the intestines and kidneys. After taking at a dose of 80 mg of 14C-labeled febuxostat, approximately 49% is eliminated by the kidneys: in the form of acylglucuronide - 30%, unchanged - on average 3%, in the form of oxidized metabolites and their conjugates - 13%, in the form of other metabolites - 3% ... About 45% of febuxostat is excreted through the intestine: in the form of acylglucuronide - 1%, unchanged febuxostat - 12%, oxidized metabolites and their conjugates - 25% and other metabolites - 7%. The apparent half-life (T1 / 2) of febuxostat can be 5-8 hours.
With the course use of febuxostat, its AUC and Cmax in women were, respectively, 12 and 24% higher than in men. At the same time, the AUC and Cmax values ​​corrected for the patient's body weight were similar for both groups, as a result of which there is no need to change the dose of the agent depending on gender.

Indications for use

    chronic hyperuricemia in conditions leading to the deposition of urate crystals, including in the presence of tophi and / or gouty arthritis, including a history of data (treatment);
    hyperuricemia in adult patients receiving cytostatic therapy of hemoblastosis, with the threat of developing FRO from moderate to high - only for a dosage of 120 mg (prevention and treatment).

Contraindications

Absolute:
    glucose and galactose malabsorption syndrome, lactase deficiency, hereditary galactose intolerance (Adenuric contains lactose);
    pregnancy and lactation;
    age under 18;
    hypersensitivity to any of the constituents of the drug.
Relative (the tablets should be taken with extreme caution):
    congestive heart failure;
    ischemic heart disease (CHD);
    liver failure;
    renal failure of severe severity (CC below 30 ml / min);
    damage to the thyroid gland;
    Lesch-Nyhan syndrome (experience with the drug is limited);
    a history of allergic reactions;
    conditions after organ transplantation (experience with febuxostat therapy is limited);
    a combination with mercaptopurine / azathioprine (due to the increased risk of an increase in the plasma concentration of these substances in the blood and an increase in their toxicity).

Instructions for use: method and dosage

The tablets are taken orally 1 time per day, regardless of the time of the meal.
For the treatment of gout, the drug is recommended to be used at an initial dose of 80 mg. After 2-4 weeks after the start of the course, the serum level of uric acid in the blood should be monitored; if this indicator exceeds 6 mg / dL (357 μmol / L), the dose of febuxostat can be increased to 120 mg. Monitoring the concentration of uric acid in serum can be carried out 2 weeks after the start of treatment with the drug, since Adenuric provides a fairly rapid decrease in its level. The task of therapy is to reduce the content of uric acid in the blood serum and maintain it at a level below 6 mg / dL (357 μmol / L).
In order to prevent the occurrence of acute attacks of gout, the drug should be used for at least 6 months.
To prevent the development of hyperuricemia during cytostatic therapy of hemoblastosis with the threat of FRO and its treatment, it is recommended to start taking Adenuric 2 days before the start of the use of cytostatics. Prescribe tablets at a dosage of 120 mg, take them once a day. The course should be at least 1 week.
Taking into account the duration of chemotherapy, it is allowed to increase the duration of use of the anti-gout agent up to 9 days.

Side effects

Gout

The most common adverse reactions in patients with gout receiving Adenuric included abnormal liver function, gout attack, headache, diarrhea, nausea, edema, and skin rash. These phenomena, as a rule, differed in mild / moderate severity.
The frequency of adverse effects, determined from the results of clinical trials, taking into account the data of post-marketing use of febuxostat:
    nervous system: often - headache; infrequently - drowsiness, dizziness, change in taste perception, weakening of the sense of smell (hyposmia), decreased sensitivity to external stimuli (hyposthesia), hemiparesis, paresthesia;
    immune system: rarely - anaphylactic reactions *; hypersensitivity reactions *, which can be manifested by such symptoms as skin rashes, characterized by infiltrative maculopapular elements of the rash; skin lesions, exfoliative / generalized rash, facial edema, fever, eosinophilia, thrombocytopenia, and liver and kidney involvement (including tubulointerstitial nephritis);
    blood and lymphatic system: rarely - thrombocytopenia, pancytopenia;
    mental disorders: infrequently - insomnia, decreased libido; rarely - nervousness;
    organ of hearing and labyrinthine disorders: rarely - tinnitus;
    organ of vision: rarely - blurred vision;
    metabolism and nutritional disorders: often - gout attacks (as a rule, they occur soon after the start of the course and during the first months of therapy, later the frequency of attacks decreases); infrequently - weight gain, decreased appetite, hyperlipidemia, diabetes mellitus; rarely - increased appetite, weight loss, anorexia;
    endocrine system: infrequently - an increase in the plasma level of thyroid-stimulating hormone (TSH) in the blood;
    cardiovascular system: infrequently - a feeling of palpitations, a feeling of heat, flushing of the face, increased blood pressure, changes in the electrocardiogram (ECG), atrial fibrillation;
    liver and biliary tract: often - liver dysfunction **; infrequently - cholelithiasis; rarely - jaundice *, hepatitis, liver damage *;
    digestive tract: often - nausea, diarrhea **; infrequently - dryness of the oral mucosa, bloating, abdominal discomfort, flatulence, dyspeptic symptoms, frequent stools, constipation, abdominal pain, vomiting, gastroesophageal reflux disease; rarely - ulcerative stomatitis, pancreatitis;
    respiratory system, chest and mediastinal organs: infrequently - a feeling of discomfort in the chest area, cough, dyspnea, chest pain, upper respiratory tract infections, bronchitis;
    musculoskeletal system: infrequently - muscle tension, muscle weakness, musculoskeletal pain, muscle spasm, bursitis, myalgia, arthralgia, arthritis; rarely - muscle / joint stiffness, rhabdomyolysis *;
    skin and subcutaneous tissue: often - skin rash (including the various types of rashes listed below with a lower frequency); infrequently - pruritus, urticaria, discoloration of the skin, petechiae, skin lesions, dermatitis, papular rash, maculopapular rash, macular rash; rarely - hyperhidrosis, alopecia, itchy rash *, measles-like rash, erythematous rash, vesicular rash, follicular rash, pustular rash, exfoliative rash, severe generalized rash *, erythema, drug reaction * with systemic eosinophils; toxicodermal necrolysis * and Stevens-Johnson syndrome *, characterized by the development of a progressive skin rash in combination with bullous lesions of the mucous membranes / skin and eye irritation;
    reproductive system: infrequently - erectile dysfunction;
    general disorders: often - edema; infrequently - increased fatigue; rarely - thirst;
    kidneys and urinary tract: infrequently - pollakiuria, hematuria, proteinuria, nephrolithiasis, renal failure; rarely - urge to urinate, tubulointerstitial nephritis *;
    laboratory and instrumental studies: infrequently - an increase in the activity of amylase in the blood, a decrease in the number of platelets, a decrease in the number of lymphocytes, a decrease in the number of leukocytes, a decrease in hematocrit, a decrease in the level of hemoglobin, an increase in the plasma level of creatine and the concentration of creatinine in the blood, an increase in the content of urea in the blood plasma, an increase plasma concentration of cholesterol and triglycerides, an increase in the plasma level of potassium in the blood, an increase in the activity of lactate dehydrogenase; rarely - lengthening of the activated partial thromboplastin time, an increase in blood glucose, an increase in the activity of alkaline phosphatase (ALP) in plasma, a decrease in the level of erythrocytes.

Notes

* Adverse reactions of Adenuric, recorded during post-marketing surveillance.
** Non-infectious diarrhea and liver side effects have been reported in phase III trials, most often with colchicine and Adenuric.

Tumor disintegration syndrome

During the study of FLORENCE therapy and prevention of hyperuricemia in adult patients receiving cytostatic therapy for hemoblastosis, with the threat of FRO development, adverse events were recorded in 22 patients (6.4%). In patients from the febuxostat group and the allopurinol group, the incidence of adverse reactions was equal (11 patients each). In most cases, the side effects were mild / moderate. In total, in addition to violations of the cardiovascular system in the form of hemorrhages, sinus tachycardia, left bundle branch block, there were no features of the safety profile of the drug in addition to that against the background of gout.

Overdose

Symptoms of Adenuric overdose may include an aggravation of the adverse reactions described above.
In this condition, symptomatic and supportive therapy is prescribed.

Special instructions

The use of Adenuric should be started only after the removal of an acute attack of gout. The initiation of treatment with the drug can cause an exacerbation of the disease as a result of the release of urates from tissue depots and a further increase in the serum concentration of uric acid in the blood. In order to prevent exacerbation of gout in the absence of contraindications, the drug should be combined with the use of non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine for at least 6 months. If a gout attack occurs during the treatment with Adenuric, you should continue taking the drug and at the same time conduct appropriate treatment for its exacerbation. Against the background of prolonged use of the drug, the frequency and severity of attacks are reduced.
In patients with accelerated formation of urates (in particular, with Lesch-Nyhan syndrome or against the background of malignant tumors), in rare cases, there is a threat of a significant increase in the absolute concentration of xanthines in the urine, which can cause their deposition in the urinary tract. This phenomenon was not observed with the use of Adenuric in patients with FRO in the FLORENCE study.
Within the framework of post-marketing control, there were rare reports of the development of such serious hypersensitivity reactions as toxicodermal necrolysis, acute anaphylactic reactions / shock, Stevens-Johnson syndrome. Most of these complications occurred during the first month of drug treatment. Some patients had a history of renal impairment and / or hypersensitivity reactions to allopurinol. Severe hypersensitivity reactions in some cases were accompanied by changes in blood counts, fever, functional disorders of the liver or kidneys. Patients need to be aware of possible symptoms and signs of hypersensitivity reactions and be monitored for the development of symptoms of these complications. If the development of serious responses to therapy is observed, it is necessary to immediately stop taking Adenuric, since early cessation of its use improves the prognosis. In these cases, re-administration of febuxostat is contraindicated.
Patients who are on cytostatic therapy of hemoblastoses with the threat of developing FRO from a moderate to severe degree, in the presence of clinical manifestations from the heart while using Adenuric, need careful monitoring by a cardiologist.
In the course of long-term open studies with prolonged use of febuxostat, an increase in TSH level (> 5.5 μIU / ml) was recorded in 5.5% of patients, therefore, patients with functional disorders of the thyroid gland should take Adenuric with caution.
According to pooled data from phase III clinical trials, mild liver dysfunctions were observed in 5% of patients treated with febuxostat. Before starting treatment with Adenuric, an assessment of liver function should be carried out, and in the presence of clinical manifestations, it should be monitored periodically during the use of the drug.

Influence on the ability to drive vehicles and complex mechanisms

During therapy with febuxostat, there is a risk of dizziness, drowsiness, blurred vision and paresthesia, which can lead to a decrease in reaction and ability to concentrate. Given the likelihood of developing adverse events, patients taking Adenuric should exercise caution when driving vehicles and operating other complex and potentially dangerous machinery.

Application during pregnancy and lactation

Taking the drug during pregnancy is contraindicated due to insufficient data on the possible risk of therapy with febuxostat during this period for humans. According to the limited experience of using the drug in pregnant women, its adverse effects on pregnancy and fetal / newborn health have not been recorded. In the course of preclinical studies on animals, both direct and indirect negative effects on the course of pregnancy, the process of childbirth and the development of the embryo / fetus were not observed.
It is not known whether febuxostat is excreted in human milk. In animals, the penetration of the substance into breast milk was established and its adverse effect on the development of suckled pups was established. Due to the existing risk of excretion of the drug in breast milk, Adenuric is contraindicated for use during lactation.

Childhood use

Adenuric is not intended for use in pediatric practice.

With impaired renal function

In the presence of mild / moderate renal failure, individual selection of doses of the drug is not required. In patients with severely impaired renal function (CC <30 ml / min), the safety and efficacy of using Adenuric has not been adequately studied, and therefore it is recommended to use it with extreme caution.

For violations of liver function

When treating gout against the background of mild hepatic insufficiency - class A on the Child-Pugh scale (5-6 points), it is recommended to take febuxostat in a daily dose of 80 mg. In patients with moderate hepatic impairment, the experience of using Adenuric is limited.
In clinical trials of FLORENCE, with the threat of FRO development, it was not required to adjust the dose of Adenuric depending on the activity of the liver (patients with severe hepatic insufficiency did not participate in these studies).
The efficacy and safety of treatment with febuxostat in patients with severe class C liver dysfunction according to the Child-Pugh scale (10-15 points) has not been studied.

Use in the elderly

In elderly people, when compared with young volunteers against the background of repeated administration of febuxostat, there were no significant changes in the AUC of the drug and its metabolites. Elderly patients do not need individual selection of doses of Adenuric.

Drug interactions

    cytostatics: studies on the interaction of these agents with febuxostat have not been carried out, as a result of this, the possible interaction of the latter with simultaneously used cytotoxic drugs cannot be ruled out;
    theophylline: there were no changes in the pharmacokinetic parameters or tolerability of this substance when it was used in a single dose of 400 mg in combination with febuxostat in a daily dose of 80 mg; this combined use does not require special precautions; concomitant use of theophylline with febuxostat 120 mg has not been studied;
    rosiglitazone and other substrates of the isoenzyme CYP2C8: no change in the dose of these agents and Adenuric is required; according to in vitro data, febuxostat belongs to weak inhibitors of the isoenzyme CYP2C8, when taken at a dose of 120 mg per day and rosiglitazone in a single dose of 4 mg, no changes in the pharmacokinetic characteristics of rosiglitazone and its metabolite N-dismethyl rosiglitazone were recorded;
    inhibitors of glucuronidation, including naproxen: there was an increase in AUC, Cmax and T1 / 2 of febuxostat by 41, 28 and 26%, respectively, when the latter was combined with naproxen at a dose of 250 mg twice a day; drugs that inhibit the glucuronidation process, such as probenecid and NSAIDs, are theoretically capable of affecting the excretion of febuxostat; in the course of studies, the simultaneous use of febuxostat and naproxen or other NSAIDs / inhibitors of cyclooxygenase-2 (COX-2) did not lead to a clinically significant increase in the frequency of side effects; with this combination, there is no need to adjust the doses of drugs;
    colchicine / hydrochlorothiazide / indomethacin: there is no need to change the dose of Adenuric during combination therapy;
    warfarin: no effect on INR (international normalized ratio), factor VII activity and pharmacokinetics of warfarin when used in combination with febuxostat at a dose of 80 or 120 mg per day is recorded; dose adjustment of warfarin with this combination is not carried out;
    powerful inducers of glucuronidation: it is possible to increase the metabolic transformation of febuxostat and reduce its effectiveness; 1–2 weeks after the start of the combination therapy, it is necessary to control the serum level of uric acid in the blood; if the glucuronidation inducer is canceled, an increase in the Cmax of febuxostat may be observed;
    substrates of the CYP2D6 isoenzyme (including desipramine): febuxostat, according to in vitro data, refers to weak inhibitors of the CYP2D6 isoenzyme; while taking febuxostat in a daily dose of 120 mg, an increase in the AUC of desipramine by 22% was recorded, which is evidence of the weak inhibitory effect of febuxostat in vivo on the isoenzyme CYP2D6; no dose adjustment of the substrates of this isoenzyme and Adenuric is required;
    antacids (containing magnesium / aluminum hydroxide): there was a decrease in the absorption of febuxostat by about 1 hour and a decrease in Cmax by 32%, while the AUC of the agent did not change significantly; taking Adenuric can be combined with taking antacids.

Terms and conditions of storage

Store out of the reach of children at a temperature not exceeding 25 ° C.
Shelf life is 3 years.

Reviews

The reviews about Adenuric found on medical sites and specialized forums mainly indicate its effectiveness in the treatment of hyperuricemia in adults. Taking the drug leads to a real and rapid decrease in the concentration of uric acid in the blood. The advantages also include a convenient dosing regimen - taking 1 time per day. But the use of an anti-gout drug is recommended only as directed by the attending physician.
The disadvantages of Adenuric are its high cost, the presence of contraindications and the possible development of side effects.

Terms of sell

You don't need a prescription to buy Adenuric.