Ambiz - instructions for use, dose, side effects, contraindications

Active substanceAmphotericin BAmphotericin B

Similar drugsTo uncover

Ambiz®

powder d / infusion

Gilead Science International Co., Ltd. United Kingdom

Amphotericin B

lyophilizate d / infusion

SYNTHESIS, OJSC Russia

Dosage form: & nbspPPowder for the preparation of concentrate for the preparation of dispersion for infusions

Composition:

1 bottle contains:

active substance: amphotericin B 50 mg;

Excipients: components of liposomes - hydrogenated soybean phosphatidylcholine 213 mg, cholesterol 52 mg, distearoyl phosphatidylglycerol (sodium salt) 84 mg, alpha-tocopherol 0.64 mg, other - sucrose 900 mg, disodium succinate hexahydrate 27 mg.

Description:

Powder or porous mass of yellow color.

Pharmacotherapeutic group:Antifungal agent

ATX: & nbsp

J.02.A.A.01 Amphotericin B

Pharmacodynamics:

Mechanism of action

Amphotericin B is a macrocyclic polyene antifungal antibiotic produced Streptomyces nodosus.

Liposomes are whole spherical vesicles formed by a variety of amphiphilic substances, such as phospholipids. In contact with aqueous solutions phospholipids form bilayer membranes.

The presence of a lipophilic group in the amphotericin B molecule allows the preparation to be integrated into the lipid bilayer by liposomes.

Amphotericin B has a fungicidal or fungistatic effect, depending on the concentration in biological fluids and the sensitivity of the pathogen.It binds to sterols (ergosterols) located in the cell membrane of a fungus that is sensitive to the drug. As a result, the permeability of the membrane is violated and the intracellular components exit into the extracellular space and lysis of the fungus. Membranes of mammalian cells also contain sterols, so it is assumed that the basis of the action of amphotericin B on human cells and mushroom cells is the same mechanism.

Microbiology

Amphotericin B, an antifungal component of the drug Ambiz®, has a high activity in vitro against many species of fungi. Amphotericin B inhibits most strains Histoplasma capsulatum, Coccidioides immitis, Candida spp., Blastomyces dermatitidis, Rhodotorula spp., Cryptococcus neoformans, Sporothrix schenkii, Mucor mucedo and Aspergillus fumigatus in the concentration range of 0.03 to 1.0 μg / ml in vitro. Influence of amphotericin B on bacteria and viruses is minimal or absent.

The efficacy of Ambiz® was demonstrated in models of visceral leishmaniasis in animals (called Leishmania infantum and Leishmania donovani). When using Ambiz® in a dose of 3 mg / kg in mice infected with Leishmania infantum, all dosing regimens (3-7 doses) led to a faster cure of mice than with sodium stibogluconate; no toxicity was observed.The efficacy of Ambiz® in mice infected with Leishmania donovani, was> 5 times higher, and the toxicity was> 25 times lower than in amphotericin B.

Pharmacokinetics:

The pharmacokinetic profile of Ambiz® (in terms of total concentrations of amphotericin B in plasma) was determined in patients with malignant tumors and febrile neutropenia, as well as in patients who underwent bone marrow transplantation who received 1-hour infusions of Ambiz® at a dose of 1.0-7.5 mg / kg / day for 3-20 days.

Ambizom® pharmacokinetic profile of the drug is significantly different from the published literature data for conventional amphotericin B. Moreover, in comparison with the conventional form of Amphotericin B after administration Ambizom® have higher maximum concentrations of Amphotericin B in plasma (C_mOh) and a large area under the concentration-time curve (AUC_0-24).

After the administration of the first and last dose of Ambiz®, the pharmacokinetic parameters (mean ± standard deviation) were in the following range:

FROM_mOh: from 7.3 μg / ml (± 3.8) to 83.7 μg / ml (± 43.0)

Half-life (T_1/2): from 6.3 h (± 2.0) to 10.7 h (± 6.4)

AUC₀_-₂₄: from 27 μg * h / ml (± 14) to 555 μg * h / ml (± 311)

Clearance (Cl): from 11 ml / h / kg (± 6) to 51 ml / h / kg (± 44)

Volume of distribution (Vss): from 0.10 l / kg (± 0.07) to 0.44 l / kg (± 0.27)

The minimum and maximum values of pharmacokinetic parameters do not always correspond to the lowest and highest doses. After the administration of Ambiz®, a rapid attainment of the equilibrium state (usually within 4 days from the start of treatment) was observed.

The pharmacokinetics of Ambiz® after the administration of the first dose is non-linear, since the increase in serum amphotericin B concentrations exceeds that for a directly proportional relationship. The marked disproportionality is probably a consequence of the saturation of the reticuloendothelial system and, accordingly, the inhibition of clearance. There was no significant cumulation of the drug in the plasma after its repeated administration at a dose of 1-7.5 mg / kg / day. Values of the volume of distribution after the first administration to achieve an equilibrium concentration of the drug in the blood suggests an extensive distribution of the drug across the tissues.

After repeated administration of Ambiz®, the elimination half-life (t_1/2_β) was approximately 7 hours.

Excretion of Ambiz® was not studied.The pathways of metabolism of amphotericin B and Ambiz® are unknown.

Due to the large size of liposomes, glomerular filtration and renal clearance of Ambiz® are absent, which avoids the interaction of amphotericin B with the cells of the distal tubules and reduces the risk of nephrotoxicity observed with the usual dosage form of amphotericin B.

Impaired renal function

The effect of renal dysfunction on the pharmacokinetics of Ambiz® was not studied. The data indicate that patients who are on hemodialysis or filtration do not need a dose change, but Ambiz® should be avoided during the procedure.

Indications:

- Systemic fungal infections due to sensitive types of pathogens, such as cryptococcosis, North American blastomycosis, disseminated candidiasis, coccidioidomycosis, aspergillosis, histoplasmosis, mucormycosis, and also some cases of American leishmaniasis of the skin and mucous membranes;

- empirical therapy in patients with a presumed fungal infection, with symptoms of febrile neutropenia, if treatment with antibacterial drugs did not yield a positive result.

- treatment of visceral leishmaniasis.

Contraindications:

- Hypersensitivity to the active substance or any other component of the drug;

- Ambiz® contains soybean oil. Do not use this medication if the patient has allergies to peanuts or soy;

- Children under 1 month.

Carefully:

-In patients with diabetes mellitus;

- in patients with a background of leukocyte transfusion or soon after it;

- in patients taking drugs simultaneously. possessing nephrotoxic action;

- in patients taking drugs simultaneously, which can reduce the level of potassium;

- in patients taking other antifungal drugs;

- during pregnancy and during breastfeeding;

- in patients with impaired renal function.

Pregnancy and lactation:

Pregnancy

Studies of teratogenicity in rats and rabbits led to the conclusion that Ambiz® does not have a teratogenic potential in these animal species.

The safety of Ambiz® in pregnant women has not been established. The drug Ambiz® should be used during pregnancy only if the possible benefit exceeds the potential risks for the mother and fetus.Treatment of systemic fungal infections in pregnant women has been successfully performed with the usual dosage form of amphotericin B without obvious effects on the fetus, but this clinical experience is not enough to draw conclusions about the safety of Ambiz® during pregnancy.

Breastfeeding period

It is not known whether amphotericin B penetrates liposomal into breast milk. The decision to breastfeed during the use of Ambiz® should be taken in consideration of the potential risk to the child, as well as the benefits of breastfeeding for the baby and the benefits of therapy for the mother.

Dosing and Administration:

Only for intravenous infusion!

Before the first use of Ambiz® to determine potential hypersensitivity to the drug and before continuing to administer its full dose, the patient is recommended to enter a minimum of recommended therapeutic doses of the drug. This test dose (1 mg / kg body weight) should be administered slowly over 10 minutes, followed by monitoring the patient for 30 minutes.

The drug Ambiz® should be administered intravenously drip for 30-60 minutes.For doses above 5 mg / kg / day, the duration of intravenous infusion should be more than 2 hours (see section "Special instructions"). The recommended concentration for intravenous infusion is 0.20 mg / ml to 2.00 mg / ml amphotericin B in the form of Ambiz.

Doses

Adult patients

Doses of Ambiz® are selected individually depending on the specific characteristics of each patient.

- For systemic fungal infections caused by sensitive types of pathogens such as cryptococcosis, North American blastomycosis, disseminated candidiasis, coccidioidomycosis, aspergillosis, histoplasmosis, mucomycosis, and in some cases American leishmaniasis of the skin and mucous membranes, treatment usually starts at a daily dose of 1, 0 mg / kg body weight, which, if necessary, gradually increase to 3.0 mg / kg. The standard maintenance dose of Ambiz® is 1.0-3.0 g for 3-4 weeks.

- Empirical therapy in patients with a presumed fungal infection, with symptoms of febrile neutropenia, if antibiotic treatment has not been successful, should be started with a dose of Ambiz® 1.0 mg / kg / day; if necessary, the dose of the drug may be increased to 3.0 mg / kg / day.

- For the treatment of visceral leishmaniasis, a dose of 1.0-1.5 mg / kg / day for 21 days or a dose of 3.0 mg / kg / day for 10 days is applied. To treat patients with impaired immunity (eg, HIV-positive), a dose of 1.0-1.5 mg / kg / day can be used for 21 days. However, due to the risk of relapse, supportive therapy or repeated courses of treatment may be required.

Pediatric Use

Systemic fungal infections and a presumptive fungal infection with symptoms of febrile neutropenia in pediatric patients have been successfully treated with Ambiz®, with no unusual side effects noted. The drug Ambiz® was studied in patients aged from one month to 18 years. The dose of the drug should be calculated in the same way as for adults, per kilogram of body weight. The safety and efficacy of Ambiz® in children under the age of 1 month has not been established.

Special patient groups

Elderly patients

Changing the dose or frequency of dosing is not required.

Impaired renal function

In clinical trials, Ambiz® was administered to patients with an existing renal dysfunction in doses of 1.0-5.0 mg / kg / day; a change in dose or frequency of administration was not required.

Impaired liver function

There is no data to recommend a dose for patients with impaired liver function.

Instructions for reconstitution and dilution of Ambiz®

Recovering the concentrated dispersion Ambizom® preparation should be carried out with water for injection (WFI) (without preservatives) with further dilution in dextrose for infusion of different concentrations (5%, 10% or 20%).

Using other solutions for the recovery and formed the subsequent dilution of the concentrate, as well as the presence of preservatives in these solutions (e.g., benzyl alcohol) can cause precipitate to form.

Preparation of the reconstituted dispersion concentrate of Ambiz®

1. Add 12 ml of water for injection (WFI) in each vial with a preparation to produce a concentrate containing 4 mg / ml of amphotericin B liposomal.

2. Immediately after the addition of water for injection for 30 seconds vigorously shaken to fully disperse VIALS lyophilizate. After recovery the concentrate is translucent yellow dispersion with pH value between 5 and 6. The contents of the vial are checked for the presence of suspended particles and continue agitation until a homogenous dispersion.Do not use if there are undispersed agglomerates and (or) visible mechanical inclusions.

Preparation of Ambiz® dispersion for infusion

1. Calculate the amount of the reconstituted (4 mg / ml) dispersion of the preparation for its further dilution (see Table 1).

2. The infusion solution is prepared by diluting the reconstituted drug dispersion concentrate using 1 to 19 parts by volume of a dextrose solution for infusions (5%, 10%, or 20%) to obtain the final recommended concentration of amphotericin B in the range of 2.00 mg / ml to 0.20 mg / ml (see Table 1).

3. Collect the calculated volume of the reconstituted dispersion concentrate of Ambiz® in a sterile syringe. Through a filter (5 μm) supplied with the preparation, Insert the concentrate into a sterile infusion container pre-filled with the calculated amount of dextrose solution for infusions at the desired concentration (5%, 10%, or 20%).

For intravenous infusion of the drug, an integrated membrane filter can be used. However, the average pore diameter of the filter must not be less than 1.0 micron.

AT the table below is presented example preparation of Ambiz® dispersion for infusion in a dose 3 mg / kg / day in a 5% solution of dextrose for infusion. If a patient has been given a dose, different from the dose 3 mg / kg / day, necessary yourself doing new calculation.

Table 1. Example of preparation of Ambiz® dispersion for infusion at a dose of 3 mg / kg / day in a 5% solution of dextrose for infusion

Weight bodies the patient (kg)	Number bottles, necessary for cooking doses	Ambiz®, necessary for the patient (for filling for further dilution) (mg)	Scope reconstituted Ambiz® (for filling for further dilution (ml))	To achieve a final concentration of 0.2 mg / ml (dilution 1 in 20)		To achieve a final concentration of 2.0 mg / ml (dilution 1 in 2)
				Scope the required 5% dextrose (ml)	Total volume (ml of Ambiz® plus 5% dextrose)	Scope the required 5% dextrose (ml)	Total volume (ml, Ambiz® plus 5% dextrose)
10	1	30	7,5	142,5	150	7,5	15
25	2	75	18,75	356,25	375	18,75	37,5
40	3	120	30	570	600	30	60
55	4	165	41,25	783,75	825	41,25	82,5
70	5	210	52,5	997,5	1050	52,5	105
85	6	255	63,75	1211,25	1275	63,75	127,5

* To prepare a dose for the patient, not all the contents of the vial (s) may be required.

Special conditions for storage and treatment of reconstituted and diluted products

Since Ambiz ® is NOT compatible with 0.9% sodium chloride solution, it can not be administered with an infusion system that was previously used for 0.9% sodium chloride solution without prior washing with dextrose solution (5%, 10% or 20% ) for infusion.If this is not practical, Ambiz® should be administered via a separate system.

DO NOT mix Ambiz® with other drugs or electrolytes.

Only for single use.

Any unused contents or waste materials should be disposed of in accordance with local requirements.

Conditions of drug storage, reconstituted with water for injection

If recovery and dilution are carried out in controlled and validated aseptic conditions, the following data can be used to determine the conditions and duration of storage.

Glass bottles: 24 hours at 25 ± 2 ° C under the influence of ambient light.

Glass bottles: up to 7 days at 2-8 ° C.

Polypropylene syringes: up to 7 days at 2-8 ° C.

Do not freeze.

The shelf life of the drug reconstituted with water for injection and then diluted in dextrose

Chemical and physical stability were demonstrated under the following storage conditions using dextrose solutions as a dilution medium in PVC or polyolefin infusion bags.

Table 2.Stability of the drug reconstituted with water for injection and then diluted in dextrose

Diluent	Dilution	The concentration of amphotericin B (mg / ml)	Maximum shelf life at 2-8 ° С	Maximum shelf life at 25 ± 2 ° С
	1 in 2	2,0	7 days	48 hours
5% dextrose	1 in 8	0,5	7 days	48 hours
	1 to 20	0,2	4 days	24 hours
10% dextrose	1 in 2	2,0	48 hours	72 hours
20% dextrose	1 in 2	2,0	48 hours	72 hours

A drug reconstituted with water for injection

The drug Ambiz ® is a sterile single-dose lyophilizate without preservatives. Thus, from the microbiological point of view, the drug must be used immediately after reconstitution. If the drug has not been used immediately after reconstitution, the user is responsible for the timing and conditions for storing the drug prior to use. Typically, the shelf life does not exceed 24 hours at 2-8 ° C, except when the reconstitution and dilution of the drug was carried out under controlled and validated aseptic conditions.

Side effects:

The following undesirable drug reactions (NLR) were registered amid the use of Ambiz® in clinical trials and post-marketing periods.The frequency of HLR was determined in view of the combined data of clinical trials involving 688 patients treated with Ambiz. The frequency of NLR in the post-marketing period is unknown.

HLR are presented in the form of preferred terms MedDRA in accordance with the classification of systems and bodies MedDRA and frequency.

The frequency was determined as follows:

Often	(≥ 1/10)
Often	(from≥1 / 100 to <1/10)
Infrequently	(from≥1.1000 to <1/100)
Rarely	(< 1/10 000)
Frequency unknown	(can not be determined from available data).

NLR in each group with the indicated frequency are presented in order of decreasing severity.

Violations of the blood and lymphatic system

Infrequently: thrombocytopenia.

Frequency unknown: anemia.

Immune system disorders

Infrequently: anaphylactoid reaction.

Frequency unknown: anaphylactic reactions, hypersensitivity.

Disorders from the metabolism and nutrition

Often: hypokalemia.

Often: hyponatremia, hypocalcemia, hypomagnesemia, hyperglycemia.

Disturbances from the nervous system

Often: headache.

Infrequently: convulsions.

Heart Disease

Often: tachycardia.

Frequency unknown: cardiac arrest, arrhythmia.

Vascular disorders

Often: Arterial hypotension, vasodilation, "hot flashes" of blood.

Disturbances from the respiratory system, chest and mediastinal organs

Often: dyspnea.

Infrequently: bronchospasm.

Disorders from the gastrointestinal tract

Often: nausea, vomiting.

Often: diarrhea, abdominal pain.

Disturbances from the liver and bile ducts

Often: deviation of functional liver samples, hyperbilirubinemia, increased activity of alkaline phosphatase.

Disturbances from the skin and subcutaneous tissues

Often: rash.

Frequency unknown: angioedema.

Disturbances from musculoskeletal and connective tissue

Often: backache.

Frequency unknown: rhabdomyolysis (associated with hypokalemia), musculoskeletal pain (described as arthralgia or bone pain).

Disorders from the kidneys and urinary tract

Often: increasing the concentration of creatinine, increasing the concentration of urea blood.

Frequency unknown: renal insufficiency.

General disorders and disorders at the site of administration

Often: trembling, hyperthermia.

Often: chest pain.

Infrequently: phlebitis.

Laboratory results

False positive results of the study of serum phosphorus concentration in the analysis of samples of patients receiving Ambiz preparation, using quantitative analysis PHOSm (for example, used in analyzers Beckman Coulter, including Synchron LX20). This quantitative analysis is intended for the quantitative determination of inorganic phosphorus in serum, plasma or human urine samples.

The most frequent infusion-related reactions, expected during the administration of Ambiz®, are fever and chills / shivering.

Less frequent infusion-related reactions may include one or more of the following symptoms: a feeling of heaviness or chest pain, dyspnea, bronchospasm, blood flushes, tachycardia, arterial hypotension, and musculoskeletal pain (described as arthralgia, back pain or bones). The above symptoms are quickly eliminated after discontinuation of the infusion and may not develop with each subsequent infusion or with slower administration of the drug (infusion duration of more than 2 hours).

In addition, the prevention of the development of infusion-related reactions can also be achieved through premedication.However, severe infusion-related reactions may require the complete cessation of Ambiz use.

Patients receiving treatment with Ambisome, much less marked infusion-related reaction compared to patients treated with conventional formulations of amphotericin B or amphotericin B lipid complex B.

Also, the incidence and severity of NLR with Ambiz® was less than that of conventional amphotericin B.

Most patients who received intravenously the usual form of amphotericin B showed a nephrotoxic effect of the drug of varying severity. The nephrotoxic effect of Ambiz® (an increase in the serum creatinine concentration more than 2.0 times the baseline) was recorded approximately 2 times less frequently than with the use of the usual form of amphotericin B or the amphotericin B lipid complex.

Overdose:

The toxicity of Ambiz® due to acute overdose has not been determined.

In case of an overdose, stop the injection immediately.Careful monitoring of the patient's clinical condition, including renal and hepatic function, serum electrolyte concentration and hematologic status should be carefully monitored. Hemodialysis or peritoneal dialysis does not seem to affect the excretion of amphotericin B liposomal.

Interaction:

Special studies of interaction with Ambiz® were not carried out. However, it is known that the following drugs interact with amphotericin B and can interact with Ambiz®.

Drugs with known nephrotoxicity: simultaneous use of Ambiz® with other nephrotoxic agents (eg, cyclosporine, aminoglycosides and pentamidine) may increase the risk of drug nephrotoxicity in some patients. However, in patients receiving Ambiz® along with cyclosporine and (or) aminoglycosides, nephrotoxicity was significantly less frequent than with amphotericin B.

In patients receiving Ambiz® along with other nephrotoxic drugs, it is recommended that the kidney function be monitored regularly.

Glucocorticosteroids, corticotropin (ACTH) and diuretics: simultaneous use of corticosteroids, ACTH and diuretics (loop and thiazide) can increase the severity of hypokalemia.

Glycosides of Digitalis: Ambizom-induced hypokalemia may increase the toxicity of digitalis.

Muscle relaxants: Ambiz®-induced hypokalemia may enhance the curare-like effect of muscle relaxants (eg, tubocurarine).

Antifungal means: simultaneous application with flucytosine may increase the toxicity of flucytosine by possibly increasing its capture by cells and (or) disturbing its excretion by the kidneys.

Antineoplastic agents: simultaneous use of antitumor agents may increase the risk of manifestations of nephrotoxicity, the development of bronchospasm and arterial hypotension. Concomitant use of antitumor agents requires caution.

Transfusion of leukocyte mass: cases of acute pulmonary toxicity have been described in patients who received amphotericin B (as a complex of sodium deoxycholate), during or shortly after the transfusion of leukocyte mass.It is recommended to observe the maximum possible interval between the administration of Ambiz® and the transfusion of leukocyte mass, as well as to control lung function.

Incompatibility

Do not mix Ambiz® with other medicines other than those listed under the "Application and Dosage" section.

Ambiz® is not compatible with saline solutions and should not be mixed with other drugs or electrolytes.

Special instructions:

The dosage of Ambiz® is strictly specific and can not be applied to other amphotericin B.

Ambiz® should not be used to treat common, clinically latent forms of fungal infections that are characterized only by positive skin or serological test results.

Anaphylactic and anaphylactoid reactions were reported during the infusion of Ambiz®. To assess the possibility of developing idiosyncratic anaphylactic reactions and minimizing the dose administered, if these reactions develop, initial administration of the test dose is recommended.In the case of a severe anaphylactic / anaphylactoid reaction, the infusion should be immediately interrupted without the possibility of further use of Ambiz® in this patient.

Other severe infusion-related reactions may develop during the administration of drugs containing amphotericin B, including Ambiz®. Although infusion-related reactions are generally not serious, certain precautions should be taken for both prevention and treatment of these reactions in patients receiving Ambiz®. It is noted that a decrease in the rate of drug administration (duration of infusion over 2 hours) or the use of standard doses of diphenhydramine, paracetamol, pethidine and / or hydrocortisone effectively prevents the development of these reactions or facilitates their reduction.

It was shown that the Ambiz® preparation is significantly less toxic than the usual dosage form of amphotericin B, especially in the manifestation of nephrotoxicity; However, NLR, including the kidneys, can still develop.

The results of comparative studies of Ambiz® in a daily dose of 3 mg / kg and higher doses (5,6 or 10 mg / kg / day) showed that the frequency of increase in serum creatinine, hypokalemia and hypomagnesemia was significantly higher against the background of high doses.

A laboratory evaluation of the electrolyte content in blood serum, especially potassium and magnesium, as well as kidney, liver and hematopoiesis should be performed regularly. This is especially important for patients receiving concomitant nephrotoxic drugs. Due to the increased risk of hypokalemia during treatment with Ambiz®, an adequate supply of potassium in the body may be required. In the case of a clinically significant decrease in renal function or impairment of other parameters, consideration should be given to reducing the dose, interrupting, or discontinuing Ambiz treatment®.

In the treatment of patients with diabetes, it must be borne in mind that each Ambiz® vial contains approximately 900 mg of sucrose.

In the treatment of patients who require a hemodialysis or filtration procedure, Ambiz® dosage adjustment is not required, however, it should be avoided during the procedure.

Ambiz® should not be given to patients with rare hereditary disorders, such as fructose intolerance, glucose malabsorption syndrome and galactose, or sucrose-isomaltase deficiency.

This drug contains less than 1 mmol sodium (23 mg) per vial, i. E. practically does not contain sodium.

Effect on the ability to drive transp. cf. and fur:

Studies of the impact on the ability to drive and work with mechanisms have not been carried out. Some of the undesirable effects of Ambiz® can affect the ability to drive and use machinery.

Form release / dosage:

Powder for the preparation of concentrate for the preparation of dispersion for infusion, 50 mg.

Packaging:

50 mg of active ingredient in bottles of transparent colorless glass type I with a capacity of 20 ml, sealed with rubber stoppers, sealed aluminum caps with a detachable plastic lid of the "Flip-off".

10 bottles in cardboard separators and 10 filters (5 microns) together with instructions for medical use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003614

Date of registration:12.05.2016 / 07.11.2016

Expiration Date:12.05.2021

The owner of the registration certificate:Gilead Science International Co., Ltd. Gilead Science International Co., Ltd. United Kingdom

Manufacturer: & nbsp

Gilead Sciences Ireland UC Ireland

Representation: & nbspGilead Sciencez Rasha, OOOGilead Sciencez Rasha, OOO

Information update date: & nbsp27.07.2017

Illustrated instructions

Instructions

Ambiz® (Ambisome®)