Rucectam®

Pharmacological Properties
Pharmacodynamics
Combination drug.
Ceftriaxone is a semi-synthetic cephalosporins broad-spectrum antibiotic of the III generation. Ceftriaxone bacterial growth inhibitory activity is due to synthesis suppression in cell membranes.

Sulbactam Sulbactam is an irreversible inhibitor of beta-lactamases which are effused by bacteria resistant to beta-lactam antibiotics; it prevents destruction of penicillins and cephalosporins under the action of bacteria resistant to beta-lactamases; it binds to penicillin-binding proteins and exhibits synergism when administered simultaneously with penicillins and cephalosporins.

Sulbactam has no clinically significant antibacterial activity (with the exception of Neisseriaceae and Acinetobacter). Sulbactam interacts with some penicillin-binding proteins (PBPs); that’s why the combination of Ceftriaxone+[Sulbactam] often has more marked specific effect on sensitive strains in comparison with the use of Ceftriaxone only. The combination of Ceftriaxone/Sulbactam is active against all bacteria sensitive to Ceftriaxone and acts synergistically (reduces the minimal inhibitory concentration (MIC) of the combination up to 4 times in comparison with Ceftriaxone).

It is active against the following bacteria:

Gram-negative aerobes:
Acinetobacter Iwofii, Acinetobacter baumannii*, Aeromonas hydrophila; Alcaligenes faecalis; Alcaligenes odorans; Borrelia burgdorferi; Capnocytophaga spp.; Burkholderia cepacia; Citrobacter diversus, including (Citrobacter amalonaticus), Citrobacter freundii**; Escherichia coli; Enterobacter aerogenes*, Enterobacter cloacae*; Enterobacter spp.*; Haemophilus ducreyi; Haemophilus influenzae; Haemophilus parainfluenzae; Hafnia alvei; Klebsiella oxytoca, Klebsiella pneumoniae**, Moraxella catarrhalis; Moraxella osloensis; Moraxella spp.; Morganella morganii; Neisseria gonorrhoeae; Neisseria meningitides; Pasteurella multocida; Plesiomonas shigelloides; Proteus mirabilis, Proteus penneri*, Proteus vulgaris*; Pseudomonas fluorescens*; Pseudomonas spp., Providencia spp., в т.ч. Providencia rettgeri*; Salmonella spp. (non-typhoidal), Salmonella typhi; Serratia spp.*, including Serratia marcescens*; Shigella spp.; Vibrio spp.; Yersinia spp., including Yersinia enterocolitica.

*- Some isolates of these species are resistant to Ceftriaxone, mainly, owing to formation of chromosomal beta-lactamases.
** -Some isolates of these species are resistant to Ceftriaxone owing to formation of numerous plasmid-mediated beta-lactamases.

A number of strains of the above mentioned bacteria resistant to other antibiotics, such as penicillins, cephalosporins, Aminoglycosides, are sensitive to Ceftriaxone. Treponema pallidum is sensitive to Ceftriaxone in vitro. Pseudomonas aeruginosa clinical isolates are sensitive to Ceftriaxone.

Gram-positive aerobes:
Staphylococcus aureus (including strains forming penicillinase); Staphylococcus spp. (coagulase-negative); Streptococcus pyogenes (Group A beta-hemolytic streptococcus); Streptococcus agalactiae (Group B beta-hemolytic streptococcus); Streptococcus pneumoniae-, Streptococcus spp. of viridans group.
Note: Methicillin-Resistant Staphylococcus spp. resistant to cephalosporins, including Ceftriaxone. As a rule, Enterococcus faecalis, Enterococcus faecium и Listeria monocytogenes are also resistant.

Anaerobic Micronychia:
Bacteroides spp., including Bacteroides fragilis, Clostridium spp. (sensitive to bile) with the exception of Clostridium difficile); Fusobacterium spp. (including Fusobacterium nucleatum); Peptococcus spp., Peptostreptococcus spp.* Some isolates of these species are resistant to Ceftriaxone due to formation of beta-lactamases. Pharmacokinetics
Ceftriaxone pharmacokinetics has non-linear features. All basic pharmacokinetic parameters based on the drug overall concentrations, with the exception of elimination half-life, depend on the dose and grow up less proportionately to the dose escalation. Nonlinear nature is characteristic of pharmacokinetic parameters that depend on the Ceftriaxone overall concentrations in blood plasma (aside from free Ceftriaxone); it is attributable to saturation binding of the drug with proteins present in blood plasma.
Ceftriaxone maximum concentration (Сmax) after a single intramuscular (I.M.) injection with a dose of 1.0 g is about 81 mg/L and is achieved in 2-3 hours after the injection; while Sulbactam maximum concentration is 6.24 mg/L and is achieved in about 1 hour after the injection.

Pharmacokinetics curve area, “concentration-time” (AUC) for Ceftriaxone after I.M. injection is same as for intravenous (I.V.) injection of the equivalent dose indicating 100 % bioaccessibility after the I.M. injection.

The volume of distribution (Vd) of Ceftriaxone is 7-12 L and of Sulbactam – 18.0-27.6 L.
Both Ceftriaxone and Sulbactam are adequately distributed in various tissues and body fluids, including ascitic fluid, cerebrospinal fluid (of patients with piitis), urine, saliva,amygdala,skin, Fallopian tubes, ovaries, alvus, lungs, bones, bile, bile cyst, cecal appendage. Sulbactam seeps through a placental barrier.
Ceftriaxone and Sulbactam are reversibly bound to plasma proteins by 70-90 % and 38 % accordingly.

Ceftriaxone is not subject to systemic metabolic and under the action of gut microflora turns into inactive metabolites.
Elimination half-life (Т1/2) of Sulbactam is in average about 1 hour and of Ceftriaxone- about 8 hours. Plasmatic clearance of Ceftriaxone is 10-20 mL/min; renal clearance is 5-12 mL/min.

About 84 % of Ceftriaxone dose and 50-60 % of Sulbactam doses are eliminated out of the body by kidneys (direct excretion); the remaining part of Ceftriaxone is excreted into the intestinal tract with bile.

During repeated administration of both Ceftriaxone/Sulbactam constituents no significant pharmacokinetic changes were revealed. If the drug was injected every 8-12 hours no accumulation was observed.

Penetration into cerebrospinal fluid: Ceftriaxone penetrates into spinal fluid of newborn infants and children; at that in case of bacterial meningitis, 17 % (in average) of Ceftriaxone concentration in plasma diffuse into cerebrospinal fluid, nearly 4 times as many as in case of aseptic meningitis. In 24 hours after I.V. injection of Ceftriaxone with a dose of 50-100 mL/kg of bwt, the concentrations in cerebrospinal fluid exceeds 1.4 mg/L. After injecting a dose of 50 mg/kg of bwt, in 2-24 hours, Ceftriaxone concentrations in cerebrospinal fluid of adult patients suffering from meningitis are many times higher than minimal inhibitory concentrations (MIC) in terms of the most common type of meningitis originators.

Special Subject Groups
70 % of the Ceftriaxone dose injected is eliminated out of the body by kidneys. Т1/2, in average, of newborn infants of the first 8 days of lifetime as well as of persons over the age of 75 is 2-3 times as many as of that of adults.

Ceftriaxone pharmacokinetics of patients with compromised kidney of liver function has hardly changed; there is only slight increase in Т1/2. With kidney failure only, there is increase in excretion with bile; with liver failure only, there is increase in excretion by kidney.

Patients with renal compromises showed high correlation between the total body clearance of Sulbactam and the calculated creatinine clearance. Patients with terminal renal insufficiency revealed Т1/2 significant lengthening of Sulbactam (to 9.7 hours). Haemodialysis caused significant changes in elimination half-life, the total body clearance and volume of Sulbactam distribution.

Indications for Use
Infectious and inflammatory diseases caused by pathogens sensitive to Ceftriaxone+Sulbactam combination: kidney and urinary tract infections
–    Abdominal cavity organs infections (peritonitis, infections of biliary tract & gastrointestinal tract)
–    Respiratory tract infections, especially pneumonia
–    Infection of Ear Nose Throat (ENT) organs (including acute otitis media)
–    Bacterial meningitis
–    Septicemia
–    Endocarditis
–    Bone and joint infections
–    Skin and soft tissue infections, as well as wound fever
–    Lyme disease
–    Genital infection, including uncomplicated gonorrhea
–    Infections of patients with weakened immune systems
Perioperative infection prevention

Contraindications
Hypersensitivity to Sulbactam and Ceftriaxone as well as to other cephalosporins, penicillins, beta-lactam antibiotics, hyperbilirubinemia or icterus of mature newborn infants, premature newborns under the “expected” age of 41 weeks (with the consideration of intrauterine growth duration and age); mature newborn infants with indication of intravenous injections of calcium solutions; acidosis, hypoalbuminemia of mature newborn infants.

Lidocaine
Prior to I.M. injection of Ceftriaxone with the use of lidocaine contraindications available to lidocaine should be excluded. Contraindications to lidocaine use are specified in the Instructions for medical use of lidocaine. It is prohibited to inject intravenous (I.V.) the drug solution prepared with the use of lidocaine solutions.

With caution
In case of ulcerative colitis, with compromised liver or kidney function, in case of enteritis and colitis connected with the administration of antibacterial drugs.

Use During Pregnancy and Breastfeeding
Administration during pregnancy is possible only if the potential benefit for the mother outweighs the potential risk to the fetus (Ceftriaxone and Sulbactam seep through a placental barrier). If administration of the drug during lactation is necessary, breastfeeding should be terminated.

Administration and Dosage
Intravenously or intramuscularly.
For adults and children over the age of 12 whose body weight (bwt) exceeds 50 kg: Ceftriaxone dose is 1-2 g (Sulbactam dose is 0.5-1 g) once a day or divided into two injections (every 12 hours).

For severe cases or infections, pathogens of which have moderate sensitivity to Ceftriaxone, a daily dose may increased to 4 g of Ceftriaxone. The maximum daily dose of Sulbactam is 4 g.

Duration of treatment should depend on the disease progress. The drug injection should not be discontinued at least for more 48-72 hours at normal body temperature and after confirmation of eradicating the pathogen.

The course of treatment is usually 4-14 days; in case of complicated infections additional injection of the drug may be required.
The course of treatment in case of infections caused by Streptococcus pyogenes should be at least 10 days.
Patients with compromised kidney function there is no need for dose reduction if liver function is still normal. In case of renal insufficiency (with Creatinine clearance (CLCR) less than 15 mL/min), a daily dose should not exceed 2 g of Ceftriaxone and 1 g of Sulbactam.

Patients with compromised liver function there is no need for dose reduction if kidney function is still normal.
If renal insufficiency and hepatic insufficiency are combined, it is necessary to determine the Ceftriaxone concentration in plasma on regular basis and adjust its dosage in case of need. If the Ceftriaxone concentration in plasma is not determined, a daily dose should not exceed 2 g of Ceftriaxone.
For patients kept on haemodialysis there is no need for an additional dose after haemodialysis session; however, it is necessary to exercise control over Ceftriaxone concentration in plasma since its elimination out of the body of these patients may slow off (dose adjustment may be required).
Elderly patients: ordinary doses for adults without adjustment for age provided that there is no severe renal or hepatic insufficiency.

Newborn infants, children at the breast and children to 12 years old
if the drug is administered once a day it is recommended to observe the following dose schedule:
–    Newborn infants (to 14 days): 20-50 mg/kf of bwt of Ceftriaxone (10-25 mg/kg of Sulbactam) once a day. A daily dose of Ceftriaxone should not exceed 50 mg/kf of bwt.
–    Newborn infants, children at the breast and children of tender years (from 15 days of lifetime to 12 years): a recommended daily dose of Ceftriaxone should be 20-80 mg/kg (10-40 mg/kg of Sulbactam) once a day or divided into 2 administrations (every 12 hours). The total daily dose of Ceftriaxone for children should not exceed 2 mg/kg/day; the maximum daily dose of Sulbactam should not exceed 80 mg/kg.
–    For children with a body weight (bwt) of 50 kg and more doses for adults should be prescribed.
Children at the breast and children to 12 years old should be injected intravenous dropwise by 50 mg/kg doses for at least 30 minutes. Newborn infants should be injected intravenous for 60 minutes in order to mitigate a risk of kernicterus pathological process.

Bacterial meningitis
If children at the breast and children of tender years suffer from Bacterial meningitis, their treatment should be commenced with a dose of 100 mg/kg of Ceftriaxone (but NMT 4 g) once a day (50 mg/kg of Sulbactam, but NMT 2 g). When the pathogen is identified and its sensitivity is determined, the dose may be increased. In case of meningococcal meningitis, the best results were reached in 4 days; in case of meningitis caused by Haemophilus influenzae -6 days; Streptococcus pneumoniae -7 days.

Lyme disease (borreliosis)
For adults and children – 50 mg/kg of Ceftriaxone (the max. daily dose- 2 g) once a day within 14 days.
Uncomplicated gonorrhea (caused by penicillinase forming and non penicillinase forming strains): a single intramuscular injection of 250 mg of Ceftriaxone for adults and children over the age of 12 with a bwt of ≥ 50 kg.

Acute otitis media
For children treated for acute otitis media, a single intramuscular injection of 50 mg/kg (but NMT 1 g) of Ceftriaxone is recommended.
Perioperative infection prevention: depending on infectious risk level, 1-2g of Ceftriaxone is injected (0.5-1 g of Sulbactam) as a single dose 30-90 minutes prior to starting a surgery operation. In case of colon or rectum surgery, simultaneous (but nor separate) injections of Ceftriaxone + Sulbactam and one medicinal product out of 5-nitroimidazole group (e.g. ornidazole) proved their worth.

Preparation and Injection of S the Drug Solutions:
Use freshly prepared solutions only.

For intramuscular injection: a vial content (1.5 g) should be dissolved in 3.5 mL of 1 % lidocaine solution. Each ml of the solution prepared contains about 250 mg equivalent to Ceftriaxone.

A more diluted solution may be used in case of need. The drug should be injected into a relatively larger muscle as with other intramuscular injections; a trial aspiration helps to prevent unintentional injection into a blood vessel. It is recommended to inject NMT 1,000 mg of Ceftriaxone (and 500 mg of Sulbactam) into one relatively larger muscle.

It is prohibited to inject intravenous (I.V.) the drug solution prepared with the use of lidocaine solutions!

For intravenous injections: a vial content should be dissolved in 10 mL of injection grade water. Each ml of the solution prepared contains about 100 mg equivalent to Ceftriaxone. The solution obtained should be injected slowly within 2-4 minutes into a major vein.

Intravenous infusion: the solution should be injected within at least 30 minutes. To prepare the solution, 2 g of Ceftriaxone (1 g of Sulbactam) should be diluted in 40 mg of one of the following infusion solutions, free of calcium ions (0.9 % sodium chloride solution, 5 % or 10% dextroglucose solution, 6 % dextran solution in 5 % dextroglucose solution).

Drug solutions should neither be mixed nor add to the solutions containing other antimicrobial drugs or other solvents, with the exception of those mentioned above, due to their incompatibility.

Adverse Effects
Allergic reactions: ardor or rigor, anaphylactic and anaphylactoid reactions (e.g. bronchismus), rash, pruritus, allergic dermatitis, urticaria, hydrops, exudative erythema multiforme, malignant exudative erythema (Stevens-Johnson syndrome), Lyell’s syndrome, allergic pneumonitis, serum disease, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Jarisch-Herxheimer type reaction.

Nervous System Disorders: headache, faintness, convulsions, vertigo, encephalopathy, bilirubin encephalopathy.

Gastrointestinal disorders: abdominal pain, diarrhea, nausea, vomiting, taste perversion, dyspepsia, drum belly, stomatitis, glossitis, pancreatitis, pseudomembranous colitis.
Hepatobiliary disorders: cholelithiasis, gallbladder “sludge”, icterus.

Hematopoietic & Lymphatic System Disorders: hemolytic anemia (including hemolytic anemia), leukopenia, lymphopenia, lymphocytosis, high lymphocyte count, monocytosis, neutropenia, thrombocytopenia, thrombocytosis, eosinophilia, granulocytopenia, basophilia, prothrombin time increase (decrease), thromboplastin time increase, agranulocytosise.

Renal and Urinary Disorders: genital fungal infections, oliguria, vaginitis, nephrolithiasis.

Local Reactions: in case of I.V. injection- phlebitis, pain, vein-track induration; in case of I.M. injection-pain, warm feeling, congestion or induration at the injection site.

Laboratory parameters: elevated liver transaminase levels or elevated alkaline phosphatase levels; hyperbilirubinemia, hypercreatininemia, increase in urea concentration, urine deposits, glycosuria, haematuria.

Others: diaphoresis, blood “hot flushes”, nasal hemorrhage, heart consciousness,     precipitate formation in lungs,     superinfection.

Overdosage
Symptoms: neurological disorders to the extent of convulsions
Treatment: overdosage should be treated symptomatically/ There is no specific antidote.
Haemodialysis and peritoneal dialysis are not effective.

Interactions with Other Drugs
Bacteriostatic antibiotics reduce bactericidal effect of Ceftriaxone and Sulbactam.
Chloramphenicol antagonism in vitro.

Pharmaceutical interactions
Ceftriaxone/Sulbactam solutions should be i mixed or injected simultaneously with other antimicrobial drugs The drug is pharmaceutically incompatible with solutions containing calcium ions (including Hartman’s and Ringer’s solutions) -precipitates may be formed -as well as solutions containing amsacrine, vancomycin, fluconazole, Aminoglycosides Ceftriaxone is free of N-methylthiotetrazole-containing group; that’s why its simultaneous use with ethanol does not lead to development of disulfiram-like reactions characteristic of some cephalosporins.
During simultaneous use of Ceftriaxone large doses and “loop” diuretics (e.g.furosemide) there were no kidney failures. There are no indications relative to increase in Aminoglycosides renal toxicity by Ceftriaxone. Probenecid does not affect Ceftriaxone elimination.

Ceftriaxone and Aminoglycosides have synergism against many gram-negative bacteria. In spite of the fact that greater efficiency of such combinations is not always anticipated, it should be kept in mind due to severe life-threatening infections, such as infections caused by Pseudomonas aeruginosa.

Ceftriaxone reduces the effectiveness of oral contraceptives; that’s why it is recommended to administer additional non-hormonal contraceptive agents. Precipitates of Ceftriaxone calcium salts may be formed if the drug is mixed with calcium solutions when one venous access is available. It is prohibited to use the drug simultaneously with calcium solutions for I.V. injections including those with long term infusions of calcium solutions, e.g.parenteral feeding with the help of Y-connector. For all groups of patients, with the exception of newborn infants, sequential administration of the drug and calcium solutions is possible if thorough washing of infusion systems is ensured between injections by compatible fluids. In vitro studies with the use of adult blood plasma and newborn infant’s cord blood plasma reveal higher risk of Ceftriaxone calcium salts formation of newborns (see “Administration and Dosage” section and “Contraindications” section).

If vitamin K antagonists are used during Ceftriaxone therapy, risks of hemorrhage increase. It is necessary to exercise regularly control over blood coagulation parameters and in case of need adjust a dose of anticoagulants during both the drug therapy and upon completion of such therapy.

Special instructions
The cases of development of serious anaphylactic reactions (hypersensitivity) were reported with regard to those patients who administered beta-lactam antibiotics such as cephalosporins. Risks of hypersensitivity reactions including those resulting in death are higher for the patients whose medical history revealed hypersensitivity reactions to many allergens. In connection with Ceftriaxone therapy severe skin adverse reactions were reported (Stevens-Johnson syndrome or Lyell’s syndrome/toxic epidermal necrolysis), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), these reactions may be .life-threatening or fatal; however, such cases frequency is still unknown. In case of allergic reaction occurrence, it is necessary to discontinue the drug and prescribe an adequate therapy.

In case of severe anaphylactic reactions urgent introduction of epinephrin should be ensured. Gluco-corticosteroid s should be injected intravenously and patency of airways, including intubation, should be ensured.

If Aminoglycosides are used simultaneously it is necessary to exercise control over kidney function. If severe renal insufficiency and hepatic insufficiency are combined, as well as for patients kept on haemodialysis, it is necessary to determine the Ceftriaxone concentration in plasma on regular basis.

In the course of long term treatment it is necessary to exercise control over peripheral blood pattern and liver/kidney function parameters on regular basis.

On rare occasions, ultrasound investigations of gall bladder revealed shadows (precipitates of Ceftriaxone calcium salts) that disappeared after treatment cessation. If symptoms or markers develop, thus indicating possible gall bladder disease or in case of gallbladder “sludge” signs during US investigations it is recommended to discontinue injection of the drug.
Some cases of pancreatitis developed during administration of the drug (likely because of bile duct obstruction) were reported. The majority of patients had risk factors of     engorgement in biliary tract (prior therapy by the drug; severe associated diseases, total parenteral nutrition); at that potential trigger of precipitate formation in the biliary tract under the action of Ceftriaxone could not be excluded.

Rare cases with changes in prothrombin time when the drug was administered were reported. Patients with vitamin K deficiency( synthesis disturbance, nutritional disorder) may require control over prothrombin time and in this case vitamin K (10 mg/week) should be prescribed if prothrombin time increases prior to or in the course of therapy. Cases of fatal reactions resulted from Ceftriaxone-calcium precipitates in newborn lungs and kidneys) were reported.  In theory, there is an interaction probability between Ceftriaxone and calcium solutions for I.V. injections of other year classes; that’s why Ceftriaxone should not be mixed with calcium solutions (including those for parenteral nutrition); it should be injected simultaneously including through separate infusion accesses in various areas. Theoretically based on Ceftriaxone T1/2 calculation, the interval between injections of Ceftriaxone and calcium solutions should be at least 48 hours. There is no data on possible interaction between Ceftriaxone and peroral calcium-containing drugs as well as between Ceftriaxone for I.M. injections and calcium-containing drugs (I.V. and peroral).

If the drug is administered both in the course of therapy and in 2-3 weeks after treatment cessation diarrhea caused by Clostridium difficile (pseudomembranous colitis.) may develop. If these phenomena occur in mild cases, it is sufficient to discontinue treatment and use ion-exchange resins (colestyramine, colestipol), in severe cases, compensation for the loss of fluid, electrolytes and protein together with vancomycin & metronidazole ingestion should be prescribed. Do not use drugs that inhibit intestinal motility.

If Ceftriaxone (or any other antibiotics) is administered, superinfection may develop; in this case the drug administration should be discontinued and relevant treatment should be prescribed.

Ceftriaxone is able to displace total bilirubin from serum albumin linkage.

As with administration of other cephalosporins, autoimmune hemolytic anemia may develop in the course of treatment by the drug. Cases of severe hemolytic anemia of adults and children were reported including fatal cases. In the event of anemia occurrence, it is necessary to discontinue treatment with the drug.

Some patients may develop Jarisch-Herxheimer ((JHR)) type reaction caused by spirochetes shortly after the start of Ceftriaxone therapy. JHR is usually a self-limiting condition or may be monitored with the help of symptomatic treatment. If such reaction develops, antibiotic therapy should not be terminated.

If patients are treated with Ceftriaxone Coombs’ test false-positive results may be recorded. As with other antibiotics, Ceftriaxone may deliver false-positive results in terms of galactosemia test. False-positive results may be obtained during urine glucose test (non-enzymatic methods); that’s why in the course of Ceftriaxone therapy glycosuria should be determined by enzymatic methods only in case of need. Ceftriaxone may cause false decrease in hypoglycemic and hyperglycemic ranges obtained with the help of some monitoring devices for glucose content in blood (see Instructions for use of the device). If necessary, alternative methods should be used to determine glucose content in blood

Effects on the Ability to Drive and Use Machines
With the consideration of adverse reaction profiles, during the treatment it is necessary to be careful when driving vehicles and operating machines as well as being busy with other potentially dangerous types of activities that require special care and quick psychomotor actions.

Dispensing Form
Powder for the preparation of a solution for intravenous and intramuscular administration, 1,000 mg + 500 mg.
The drug quantity containing 1,000 mg + 500 mg, of the active substances should be placed in vials made of transparent glass of the 1st hydrolytic class with a capacity of 10 or 20 ml, hermetically sealed with medical rubber stoppers, crimped with aluminum caps or caps combined with plastic “flip-off” covers.
1 vial with the drug and instructions for medical use should be placed in a outer carton.

For in-patient facilities:
From 10 to 50 vials with the drug with an equal number of instructions for medical use should be placed in a cardboard box.

Storage Conditions
In places protected from the light at a temperature not exceeding 25 °C.
Keep out of the reach of children.

Expiry Date
3 years.
Do not use after expiration date.

Drug Dispensing Terms
Dispensed as medical prescription.

Manufacturer
Ruzpharma, LLC, Russia
143132, Moscow Oblast Ruzsky District, Tuchkovo work settlement, ul. Komsomolskya, d.12, str.1.

Marketing Authorization Holder’s (MAH’s) Name and Address
AlPharma, LLC, Russia
127238, Moscow, 3 Nizhnelikhoborsky proezd,dom 1A, etazh 4, pom. X, kom. 12.
Tel.: +7(495) 744-30-00

Company Receiving Consumers’ Complaints
PHARMCOMPLIANCE PHARMACOVIGILANCE AGENCY, Limited Lability Company
117186, Moscow, ul. Nagornaya, d.15-8, pom. I, office 61.
Tel + 7 495 142 24 87 ext 7 901 369 45 95
e-mail: pv@farmakonadzor.com

Registration Manager

S.E.  Sannikova