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posaconazole | Noxafil suspension for oral administration 40 mg /ml 105 ml

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Description

Release form

oral suspension

Pharmacological action

Pharmaceutical group: Antifungal drug.

Pharmaceutical Action: Noxafil is an antifungal drug. Posaconazole inhibits the enzyme lanosterol 14β-demethylase (CYP51), which catalyzes an important biosynthesis of ergosterol, the main component of the cytoplasmic membrane of fungi. As a result of this, posaconazole has a wide spectrum of antifungal action. Active against pathogens of yeast and mold mycoses, including strains resistant to other antifungal drugs.

Posaconazole is active against Candida fungi (including Candida albicans strains resistant to fluconazole, itraconazole and voriconazole, Candida glabrata and Candida kruseiy resistant or less sensitive to fluconazole, Candida lusitaniae, resistant or less sensitive to amphotericin B), Aspergillus spp. (including Aspergillus spp. isolates resistant to fluconazole, voriconazole, itraconazole and amphotericin B). Posaconazole, unlike other azole antifungal drugs, is active against pathogens of zygomycosis (Absida spp., Mucor spp., Rhizopus spp., Rhizomucor spp.).

In vitro and in clinical studies, posaconazole has been shown to be active against the following microorganisms: Aspergillus spp. (Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, Aspergillus nidulans, Aspergillus niger, Aspergillus ustus, Aspergillus ochraceus), Candida spp. (Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis), Cryptococcus neoformans, Coccidioides immitis, Fonsecaea pedrosoi, Histoplasma capsulatum, Pseudallescheria boydii, Alternaria spp., Exophiala spp., Fusarium spp., Ramichloridium spp., Rhizomucor spp., Mucor spp., Rhizopus spp.

In in vitro experiments, posaconazole also showed activity against the following microorganisms: Candida spp. (Candida dubliniensis, Candida famata, Candida guiltiermondii, Candida lusitaniae, Candida kefyr, Candida rugosa, Candida tropicalis, Candida zeylanoides, Candida inconspicua, Candida lipolytica, Candida norvegensis, Candida cerecoccus leucidae, Candida cerecocicellida, pseudotropicalis) Pichia spp., Trichosporon spp., Aspergillus sydowii, Bjerkandera adusta, Blastomyces dermatitidis, Epidermophyton floccosum, Paracoccidioides brasiliensis, Scedosporium apiospermum, Sporothrix schenckii, Wangiella dermatitid. Apophysomyces spp., Bipolaris spp., Curvularia spp., Microsporum spp., Paecilomyces spp., Penicillium spp., Trichophyton spp. However, in clinical studies, the efficacy and safety of posaconazole in the treatment of infections caused by these microorganisms has not been studied.

In laboratory conditions, it was not possible to obtain strains of Candida albicans resistant to posaconazole. Spontaneously mutated laboratory strains of Aspergillus fumigatus, which showed a decrease in sensitivity to posaconazole, were found with a frequency of 1×10-8 to 1×10-9. Clinical isolates of Candida albicans and Aspergillus fumigatus with reduced sensitivity to posaconazole are rare. In these rare cases, there is no clear relationship between the decreased sensitivity to posaconazole and its clinical inefficiency. There are known cases of the clinical efficacy of posaconazole in case of mycoses caused by agents resistant to azole antifungal drugs or amphotericin B against which posaconazole was active in vitro. Clinical criteria for the sensitivity in vitro of any fungi to posaconazole have not been established.

In the study of combinations of posaconazole with caspofungin or amphotericin B in vitro and in vivo there was no or almost no antagonism of antifungal drugs, in some cases an additive effect was noted. The clinical significance of the results of these studies has not been determined.

Pharmacokinetics: Absorption

The duration of absorption of posaconazole is, on average, from 3 to 5 hours. Posaconazole has linear pharmacokinetics with single or multiple doses of up to 800 mg. When using posaconazole in doses of more than 800 mg / day. an increase in pharmacokinetic parameters does not occur. A change in the pH of the gastric contents does not affect the absorption of posaconazole. The separation of the daily dose of posaconazole (400 mg 2 times / day) leads to an increase in pharmacokinetic parameters by 184% compared with a single dose of 800 mg.

Compared to fasting, the AUC of posaconazole when taken with low-fat foods or dietary supplements (14 g fat) increases by about 2.6 times, and when taken with fatty foods (about 50 g fat) – 4 times.

Distribution of

Posaconazole has a large Vd (1114 L), which indicates the widespread penetration of the drug into the tissues. More than 98% of the drug binds to proteins, mainly with plasma albumin.

The equilibrium state is reached after 7-10 days of repeated use of the drug.

Metabolism

Posaconazole does not form active circulating metabolites, and its concentration is unlikely to change under the action of inhibitors of P450 isoenzymes. Of the circulating metabolites, glucononide conjugates of posaconazole and a small proportion of oxidized (via P450) metabolites make up the bulk.

Excretion

Excretion of metabolites through the kidneys and intestines is approximately 17% of the administered dose.

Posaconazole is slowly excreted, the average T1 / 2 is 35 hours (from 20 to 66 hours), and the total clearance is 32 l / h. The drug is excreted mainly through the intestines (77%), while the main part (66%) falls on the active substance. Renal clearance is an insignificant part of elimination – approximately 14% (active substance is less than 0.2%).

Pharmacokinetics in special clinical cases

After the administration of posaconazole in a daily dose of 800 mg divided into several doses, the plasma concentration of the drug in patients aged 8-17 years was comparable to that in patients aged 18-64 years (on average, 776 ng / ml and 817 ng / ml, respectively). Pharmacokinetic data for children under 8 years of age are not available.

In older people (over 65), Cmax increased by 26% and AUC by 29% compared with people aged 18-45. However, in clinical studies, the safety indices of posaconazole in young and old people were similar. Therefore, dose adjustment depending on age is not required.

The pharmacokinetics of posaconazole in men and women does not differ. There is no need to change the dose of the drug depending on gender.

A slight (16%) decrease in AUC and Cmax of posaconazole in individuals of the Negroid race was noted. Dose adjustment based on race is not required.

With a single use of posaconazole, mild and moderate renal failure (n = 18, CC> 20 ml / min / 1.73 m2) did not affect the pharmacokinetics of the drug, therefore, dose adjustment in this category of patients is not required. In patients with severe renal failure (n = 6, CC <20 ml / min / 1.73 m2), the posonazole AUC varied strongly (coefficient of variation 96%) compared with other patients with renal failure (coefficient of variation <40%). However, since the renal clearance of posaconazole is negligible, it is unlikely that severe renal failure affects the pharmacokinetics of the drug, therefore, dose adjustment is not required in this case either. In patients with hepatic insufficiency, an increase in T1 / 2 was noted (26.6 h, 35.3 h and 46.1 h for mild, moderate and severe hepatic insufficiency according to Child-Pugh, respectively), compared with patients with normal liver function (22.1 h). Due to the limited pharmacokinetic data, recommendations for dose adjustment in patients with liver failure have not been developed. Indications Prevention of invasive fungal infections with decreased immunity and increased risk of developing such infections, for example, in hematological patients with prolonged neutropenia due to chemotherapy, as well as in hematopoietic stem cell transplant recipients receiving high doses of immunosuppressive drugs. Treatment of invasive fungal infections: – invasive candidiasis or esophageal candidiasis, refractory to amphotericin B, itraconazole or fluconazole, or intolerance to these drugs – invasive aspergillosis, drug refractory to amphotericinosis s or mucormycosis), cryptococcosis, refractory to other antifungal drugs, or if they are intolerant to – fusarium, refractory to amphotericin B, or when it is intolerant – chromomycosis and mycetoma that is refractory to itraconazole or in its intolerance – coccidioidomycosis, refractory to amphotericin B, itraconazole or fluconazole, or with intolerance to these drugs. Refractoriness is the progression of infection or the lack of improvement in the patient’s condition after treatment for 7 days (for candidaemia within 3 days, for candidiasis of the esophagus within 14 days, with other forms of invasive candidiasis for 7 days). Treatment of oropharyngeal candidiasis is first-line therapy in patients with severe or immunocompromised disease who are not expected to have a significant effect from the use of topical drugs. Contraindications – combined use with ergot alkaloids (due to the risk of increasing the concentration of ergot alkaloids in the blood and the development of ergotism) – combined use with the substrates of the isoenzyme CYP3A4 with terfenadine, astemizole, cisosapridomine with increased risk of cisosapridomine pimidinim p, the concentration of these drugs in the blood, the subsequent lengthening of the QTc interval and, in rare cases, the development of ventricular tachycardia such as pirouette – combined use with HMG-CoA reductase inhibitors simvastatin lovastatin and atorvastatin (due to the risk of increasing the concentration of these drugs in the blood and the development of rhabdomyolysis) – hypersensitivity to any of the components of the drug Noxafil. Caution is advised to prescribe the drug with a history of hypersensitivity to other azole compounds, with severe liver dysfunction, congenital or acquired prolongation of the QTc interval, with cardiomyopathy, especially in combination with heart failure, sinus bradycardia, diagnosed symptomatic arrhythmias, when taken together with drugs that extend the QTc interval (other than those listed in the Contraindications section), due to the increased risk of developing cardiac arrhythmias ma. Pregnancy and lactation Information on the use of posaconazole in pregnant women is not enough. In animal studies, the toxic effect of the drug on the fetus was revealed. The potential risk to humans is unknown. Women of reproductive age are advised to use effective contraception during treatment with posaconazole. The use of posaconazole during pregnancy is contraindicated, unless the potential benefit to the mother outweighs the risk to the fetus. Posaconazole is excreted in milk in lactating rats. The excretion of posaconazole with breast milk in humans has not been studied. When prescribing posaconazole, breastfeeding should be discontinued. Special instructions Treatment should be initiated by a doctor with experience in treating systemic fungal infections. Before starting treatment, it is necessary to obtain material from the patient for microbiological and other laboratory studies in order to identify the causative agent of the disease. Treatment can be started without waiting for the results of these studies, but after receiving them, if necessary, correct antifungal therapy, if necessary. There is no information on cross-sensitivity between posaconazole and other antifungal azole compounds. Caution should be exercised when prescribing Noxafil to patients with hypersensitivity to other azoles. During treatment with posaconazole, there have been reports of changes in liver function (for example, from a mild to moderate increase in ALT, ACT, alkaline phosphatase and total bilirubin in the blood serum) during treatment with posaconazole. These reactions were observed mainly in patients with severe background diseases (for example, oncohematological), and they were not grounds for discontinuing therapy. The increase in functional liver function tests was reversible and completed after the cessation of therapy, and in some cases normalization of the functional indices was observed until the cessation of therapy. In rare cases, severe reactions from the liver with a fatal outcome have developed. Caution must be exercised when administering posaconazole to patients with severely impaired liver function. In such patients, lengthening the half-life of the drug can lead to an increase in its effect. Patients who have experienced liver dysfunction with Noxafil therapy according to laboratory tests should be monitored to prevent the development of more serious liver damage. Observation should include laboratory monitoring of liver function (in particular, determination of the level of ALT, ACT, alkaline phosphatase and total bilirubin in the blood serum). Some azole compounds cause an extended QT interval. Noxafil should not be administered together with drugs that are a substrate for the CYP3A4 isoenzyme and extend the QT interval. Caution should be exercised when prescribing Noxafil to patients with a high risk of heart rhythm disturbance, for example: – with congenital or acquired prolongation of the QT interval – with cardiomyopathy, especially in combination with heart failure – with sinus bradycardia – with diagnosed symptomatic arrhythmia with srdlp taking drugs that extend the QT interval (with the exception of those indicated in the Contraindications section). Electrolyte balance, especially potassium, magnesium and calcium, should be monitored and, if necessary, corrected before and during posaconazole therapy. Posaconazole is an inhibitor of the CYP3A4 isoenzyme and, if the patient is already taking drugs metabolized by the CYP3A4 isoenzyme, then posaconazole should only be used in special circumstances. The concentration of posaconazole can be significantly reduced when used in combination with rifamycin antibacterial agents (rifampicin, rifabutin), anticonvulsants (phenytoin, carbamazepine, phenobarbital, primidone) and cimetidine. Therefore, their combined use with posaconazole should be avoided if the benefits of the combined use do not exceed the risk to the patient. The recommended daily dose of Noxafil contains approximately 7 g of glucose. The drug should not be prescribed to patients with malabsorption syndrome (impaired glucose / galactose absorption). Data on the pharmacokinetics of the drug in patients with severe gastrointestinal dysfunction, which can lead to a decrease in the concentration of the drug in the blood (for example, with severe diarrhea or vomiting), limited. Such patients should be carefully monitored for the timely detection of a possible activation of fungal infection. Use with pediatrics Efficacy and safety of the use of Noxafil in children under 13 years of age have not been established. Influence on the ability to drive vehicles and control mechanisms There is no data on the effect of Noxafil on the ability to drive a car and other mechanisms. Composition 1 ml: – posaconazole (micronized) 40 mg Excipients: polysorbate 80, simethicone, sodium benzoate, sodium citrate dihydrate, citric acid monohydrate, glycerol, xanthan gum, liquid dextrose, titanium dioxide, cherry flavor (# 13174), purified water. Dosage and administration of The drug should be taken orally with food. Patients who cannot combine Noxafil with normal food should take the drug at the same time as taking liquid food supplements to improve the absorption of posaconazole. Before use, the suspension must be thoroughly shaken. – For the prevention of invasive fungal infections, the drug is prescribed 200 mg (5 ml) 3 times / day. The duration of prophylactic treatment depends on the duration of neutropenia in hematological patients or the severity of immunosuppression in hematopoietic stem cell transplant recipients. In patients with acute myeloid leukemia or myelodysplastic syndrome, the prophylactic treatment of Noxafil should be started several days before the expected onset of neutropenia and continued for 7 days after the increase in the number of neutrophils to more than 500 / ml. – For the treatment of invasive fungal infections that are refractory to other antifungal drugs or for intolerance to other antifungal drugs, 400 mg (10 ml) 2 times / day are prescribed. Patients who can not take the drug with food or nutritional supplements are recommended to take Noxafil 200 mg (5 ml) 4 times / day. The duration of therapy depends on the severity of the underlying disease of the patient, the severity of immunodeficiency and the effectiveness of the treatment. – For the treatment of oropharyngeal candidiasis, 200 mg (5 ml) is prescribed 1 time / day. – on the first day of treatment (introductory dose), then 100 mg (2.5 ml) 1 time / day. over the next 13 days. – For the treatment of oropharyngeal candidiasis refractory to itraconazole and / or fluconazole, 400 mg (10 ml) is prescribed 2 times / day. The duration of therapy depends on the severity of the underlying disease of the patient and the effectiveness of the treatment. Increased dose of Noxafil over 800 mg / day. does not increase the effectiveness of treatment. In case of impaired renal function, there are no changes in pharmacokinetic parameters, therefore, dose adjustment for impaired renal function is not required. In case of impaired liver function, the relevant pharmacokinetic data are limited, therefore, recommendations for dose adjustment in this group of patients have not been developed. In a small number of patients with decreased liver function, an increase in T1 / 2 of posaconazole was observed. Side effects The following are all treatment-related adverse events reported in the studies, including 2400 patients, 172 of them received posaconazole for at least 6 months, and 58 patients received posaconazole for at least 12 months. The most common adverse events were nausea (6%) and headache (6%). Serious adverse events reported (with a frequency of 1% each) in patients with invasive mycoses included changes in the concentration of other drugs, increased liver enzymes, nausea, rash, and vomiting. Serious adverse events reported (with a frequency of 1% each) in patients treated with posaconazole for the prevention of invasive mycoses included hyperbilirubinemia, increased liver enzymes, damage to hepatocytes, nausea and vomiting. A single case of the development of ventricular tachycardia of the pirouette type in a patient who was in serious condition and had multiple risk factors that together could lead to this complication, such as arrhythmia, recent cardiotoxic chemotherapy, hypokalemia, and a history of hypomagnesemia. Rare cases of the development of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have been observed mainly in patients who received cyclosporin or tacrolimus in addition to treating the underlying disease to prevent transplant rejection. Side effects of posaconazole are classified by frequency: often (> 1/100, but <1/10), infrequently (> 1/1000, but <1/100), rarely (> 1/10 000, but <1/1000) and in decreasing severity within each frequency group. From the hemopoietic system: often – neutropenia infrequently – thrombocytopenia, leukopenia, anemia, eosinophilia, lymphadenopathy rarely – hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, pancytopenia, bleeding disorder, bleeding (unspecified). From the side of the immune system: infrequently – allergic reactions rarely – Stevens-Johnson syndrome, hypersensitivity reactions. From the endocrine system: rarely – adrenal insufficiency, a decrease in the level of gonadotropins. From the side of the central nervous system: often – paresthesia, dizziness, drowsiness, headache infrequently – cramps, neuropathy, hypesthesia, tremor rarely – psychosis, depression, fainting, encephalopathy, peripheral neuropathy. From the side of the organ of vision: infrequently – blurry vision rarely – diplopia, scotoma. On the part of the hearing organ: rarely – hearing impairment. From the cardiovascular system: infrequently – prolongation of the QTc / QT interval, ECG deviations, palpitations, increased or decreased blood pressure rarely – ventricular tachycardia (including pirouette type), sudden death, cardiac and respiratory arrest, heart failure , myocardial infarction, cerebrovascular accident, pulmonary thromboembolism, deep vein thrombosis (unspecified). From the respiratory system: rarely – pulmonary hypertension, interstitial pneumonia, pneumonitis. From the digestive system: often – anorexia, vomiting, nausea, abdominal pain, diarrhea, dyspepsia, flatulence, dry mouth, bloating, increased liver function (including ALT, ACT, bilirubin, alkaline phosphatase, GGT) infrequently – ulceration oral mucosa, pancreatitis, hepatocyte damage rarely – gastrointestinal bleeding, bowel obstruction, liver failure, cholestatic hepatitis, cholestasis, hepatosplenomegaly, liver soreness, asterixis (hepatic tremor), severe fatal liver damage. Dermatological reactions: often – rash infrequently – alopecia rarely – vesicular rash. From the musculoskeletal system: infrequently – back pain. From the urinary system: infrequently – renal failure (including acute), an increase in blood creatinine rarely – interstitial nephritis, renal tubular acidosis. From the reproductive system: infrequently – menstrual irregularities rarely – pain in the mammary gland. On the part of laboratory indicators: infrequently – a change in serum concentrations of other drugs. Other: often – fever, asthenia, fatigue, electrolyte imbalance infrequently – hyperglycemia, edema, weakness, pain, chills, malaise rarely – swelling of the tongue, swelling of the face. Drug interactions Posaconazole is metabolized by glucuronidation and is a substrate for p-glycoprotein (in vitro), therefore inhibitors (verapamil, cyclosporine, quinidine, clarithromycin, erythromycin, erythromycin, rifinifinifinampin – rifinifinifinampin phenobarbital, primidone cimetidine, etc.) of this metabolic pathway can increase or decrease the concentration of posaconazole in the plasma. Efavirenz (400 mg once daily) reduces Cmax and AUC of posaconazole by 45% and 50%, respectively. Rifabutin (300 mg once daily) reduces Cmax and AUC of posaconazole by 57% and 51%, respectively. With the combined use of posaconazole and rifabutin or similar inducers (rifampicin), it is necessary to assess the benefit and risk for this patient. Phenytoin (200 mg once daily) reduces Cmax and AUC of posaconazole by 41% and 50%, respectively. With the combined use of posaconazole and phenytoin or similar inducers (carbamazepine, phenobarbital, primidone), it is necessary to assess the benefit and risk for this patient. H2-histamine receptor blockers (cimetidine 400 mg 2 times a day) or proton pump inhibitors reduce Cmax and AUC of posaconazole by 39%. The effect is associated with a decrease in the absorption of the drug against the background of a decrease in the acidity of gastric juice. With the combined use of posaconazole and cimetidine, it is necessary to assess the benefit and risk for this patient. Posaconazole (200 mg 1 time per day), being an inhibitor of CYP3A4, increases the AUC of iv iv midazolam (substrate of the isoenzyme CYP3A4) by 83%. The effect of posaconazole on the concentration of CYP3A4 substrates in plasma when they are orally administered has not been studied, but it can be expected to be more pronounced than with iv administration of substrates Caution should be exercised when co-administration of posaconazole and substrates of isoenzyme CYP3A4 administered iv or orally however, it may be necessary to reduce the dose of substrates of the CYP3A4 isoenzyme. Posaconazole increases the concentration of vinca alkaloids in the blood (vincristine, vinblastine) – the risk of a neurotoxic effect. Their combined use should be avoided if the benefits of combination therapy do not exceed its risk to a given patient. If joint use is necessary, it is recommended to adjust the dose of vinca alkaloids. Posaconazole increases Cmax and AUC of rifabutin by 31% and 72%, respectively. Their combined use should be avoided if the benefits of combination therapy do not exceed its risk to a given patient. If necessary, their combined use is recommended to control the blood formula and the appearance of side effects of rifabutin (uveitis). Posaconazole at a dose of 200 mg once a day increases the concentration of cyclosporine in the blood, which may increase the risk of serious side effects, including nephrotoxic reactions or fatal leukoencephalopathy (1 case). It is recommended to control the concentration of cyclosporin in the blood before, during and after treatment with posaconazole, changing, if necessary, the dose of cyclosporine. Posaconazole increases Cmax and AUC of tacrolimus (single dose – 0.05 mg / kg) by 121% and 358%, respectively. With their joint appointment, the dose of tacrolimus should be reduced (to 1/3 of the dose). During and at the end of their combined use, the concentration of tacrolimus in the blood should be carefully monitored and, if necessary, adjusted its dose. Posaconazole (400 mg 2 times a day for 16 days) increases Cmax and AUC of sirolimus (2 mg 1 time per day) 6.7 times and 8.9 times, respectively. With their combined use, the dose of sirolimus should be reduced (by 1/10 of the recommended). It is recommended to control the concentration of sirolimus in the blood before, during and after treatment with posaconazole. If necessary, adjust the dose of sirolimus. Posaconazole increases the content of non-nucleoside reverse transcriptase inhibitors (antiretroviral drugs that are substrates of the CYP3A4 isoenzyme). When used together, patients should be closely monitored to identify possible toxic reactions. Posaconazole increases the content of HIV protease inhibitors in the blood. The use of posaconazole (400 mg 2 times a day for 7 days) together with atazanavir (300 mg 1 time per day for 7 days) increases Cmax and AUC of atazanavir 2.6 times and 3.7 times, respectively. When ritonavir is added to this combination (100 mg ritonavir once a day for 7 days), the max and AUC of atazanavir increase 1.5 times and 2.5 times, respectively. Patients taking these drugs together with posaconazole should be closely monitored to identify possible toxic reactions. The use of posaconazole (200 mg 2 times a day for 7 days) together with midazolam (0.4 mg iv once a day) increases Cmax and AUC of midazolam 1.3 times and 4.6 times, respectively. The use of posaconazole (400 mg 2 times a day for 7 days) in conjunction with midazolam (0. 4 mg iv once a day) increases Cmax and AUC of midazolam 1.6 times and 6.2 times, respectively. Both posaconazole dosing regimens increase Cmax and AUC of midazolam administered orally at a dose of 2 mg once daily, 2.2 times and 4.5 times, respectively. The use of posaconazole in doses of 200 mg and 400 mg increases T1 / 2 of midazolam from 3-4 hours to 8-10 hours when used together. Caution should be exercised in prescribing other benzodiazepines that are metabolized by the CYP3A4 isoenzyme to patients receiving posaconazole. With the combined use of posaconazole with BMCC (diltiazem, verapamil, nifedipine, nisoldipine), it is necessary to control the adverse and toxic reactions associated with the action of BMCC and, if necessary, adjust their dose. With the combined use of posaconazole with digoxin, the concentration of digoxin may increase, which must be monitored during and after combination therapy. With the combined use of glipizide and posaconazole, a decrease in glucose concentration was noted. It is recommended to control the concentration of blood glucose in patients with diabetes who are simultaneously receiving sulfonylurea and posaconazole. In combinations of posaconazole with caspofungin or amphotericin in vitro and in vivo no antagonism was detected, in some cases an additive effect was noted. Overdose of In patients who received posaconazole in doses up to 1600 mg / day, no additional adverse events were detected compared with those who received lower doses. An accidental overdose was recorded in one patient who took Noxafil 1200 mg 2 times / day. within 3 days. Adverse events associated with an overdose in this patient were not observed. Posaconazole is not excreted by hemodialysis. Deystvuyuschee substances posaconazole Terms and conditions prescription dosage form oral suspension

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4 reviews for posaconazole | Noxafil suspension for oral administration 40 mg /ml 105 ml

  1. Grimarlon

    Great product and fast shipping! Thank you!!

  2. Heather

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  3. Damien

    Excellent transaction, thank you.

  4. Elvis

    A+ Thanks

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