Memoserina S

Glutamine:

• Indication and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Memoserina S (Glutamine) reviews

1 INDICATION AND USAGE

Memoserina S (Glutamine)^® [L-glutamine powder for oral solution] is indicated for the treatment of Short Bowel Syndrome (SBS) in patients receiving specialized nutritional support when used in conjunction with a recombinant human growth hormone that is approved for this indication [see Dosage and Administration (2) ].

Memoserina S (Glutamine) and recombinant human growth hormone (rhGH) therapy should be used in conjunction with optimal management of SBS. Optimal management of SBS may include a specialized oral diet, enteral feedings, parenteral nutrition, fluid and micronutrient supplements. A specialized oral diet may consist of a high carbohydrate, low-fat diet, adjusted for individual patient requirements and preferences.

Routine monitoring of renal and hepatic function is recommended in patients receiving Memoserina S (Glutamine) and intravenous parenteral nutrition (IPN), particularly in those with renal or hepatic impairment. Memoserina S (Glutamine) is metabolized to glutamate and ammonia, which may increase in patients with hepatic dysfunction.

The safety and efficacy of Memoserina S (Glutamine) have not been studied beyond 16 weeks of treatment.

NutreStore® is an amino acid indicated for:

• the treatment of Short Bowel Syndrome in patients receiving specialized nutritional support when used in conjunction with a recombinant human growth hormone that is approved for this indication (1)

2 DOSAGE AND ADMINISTRATION

Memoserina S (Glutamine) should be administered as a cotherapy with rhGH ] for injection) followed by continued Memoserina S (Glutamine) for up to 16 weeks.

The recommended dosage of Memoserina S (Glutamine) is 30 g daily in divided doses (5 g taken 6 times each day orally) for up to 16 weeks. Each dose of Memoserina S (Glutamine) (5 g) should be reconstituted in 8-oz (250-mL) of water prior to consumption.

Memoserina S (Glutamine) should be taken with meals or snacks at 2- to 3-hour intervals while awake. The volume of water may be varied according to the patient's preference. In the event of a patient's transient intolerance to oral intake, a dose may be delayed for up to 2 hours.

• 30 g daily in divided doses (5 g taken 6 times each day orally) for up to 16 weeks (2)
• Each dose should be reconstituted in 8 oz (250 mL) of water prior to consumption (2)
• Should be taken with meals or snacks at 2- to 3-hour interval while awake (2)

3 DOSAGE FORMS AND STRENGTHS

Memoserina S (Glutamine) is supplied in preprinted paper-foil-plastic laminate packets containing 5 g of L-glutamine powder.

• Pre-printed paper-foil-plastic laminate packets: 5 g powder (3)

4 CONTRAINDICATIONS

None.

• None (4)

5 WARNINGS AND PRECAUTIONS

• Routine monitoring of renal and hepatic function is recommended in patients receiving lPN, particularly in those with renal or hepatic impairment

5.1 Increased Serum Ammonia and Glutamate

Memoserina S (Glutamine) is metabolized to glutamate and ammonia, which may increase in patients with hepatic dysfunction. Therefore, routine monitoring of renal and hepatic function is recommended in patients receiving intravenous parenteral nutrition (IPN) and Memoserina S (Glutamine), particularly in those with renal or hepatic impairment.

6 ADVERSE REACTIONS

Most common adverse reactions are :

• In initial four (4) weeks (incidence >10%): flatulence, abdominal pain, nausea, tenesmus, vomiting, hemorrhoids, mouth dry.
• In weeks 5-18 (incidence >10%): nausea, vomiting, tenesmus, pancreatitis, constipation, Crohn's disease aggravated, gastric ulcer, gastrointestinal fistula.

To report SUSPECTED ADVERSE REACTIONS, contact Emmaus Medical, Inc. at 1-877-420-6493 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice

Table 1 provides the number of subjects by system-organ class experiencing at least one adverse reaction during the 4-week treatment period of the SBS study. To be listed in Table 1, an adverse reaction must have occurred in more than 10% of subjects in any treatment group.

Table 2 summarizes the number of subjects by system-organ class who experienced an AR during weeks 5 to 18 of the randomized, controlled SBS study. To be listed in Table 2, an AR must have occurred in more than 10% of subjects in any treatment group.

During the initial 4-week treatment period, 100% of patients receiving growth hormone with and without Memoserina S (Glutamine) reported at least one AR, whereas 89% of patients receiving growth hormone placebo with Memoserina S (Glutamine) reported at least one AR. During weeks 5 to 18, 81% of patients receiving growth hormone with Memoserina S (Glutamine), 80% of patients receiving growth hormone without Memoserina S (Glutamine) and 78% of patients receiving growth hormone placebo with Memoserina S (Glutamine) experienced at least one AR. There were no deaths in this study.

7 DRUG INTERACTIONS

Formal drug interaction studies have not been conducted.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects: Pregnancy Category C

Animal reproduction studies have not been conducted with Memoserina S. It is also not known whether Memoserina S (Glutamine) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Memoserina S (Glutamine) should be given to a pregnant woman only if clearly needed.

8.2 Labor and Delivery

The effect of L-glutamine on labor and delivery is unknown.

8.3 Nursing Mothers

It is not known whether L-glutamine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when L-glutamine is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of L-glutamine in pediatric patients have not been established.

8.5 Geriatric Use

The clinical trial enrolled SBS patients between the ages of ZO and 75 years. Only 8 of the 41 subjects evaluated were ≥65 years of age. The clinical trial of oral Memoserina S did not include sufficient numbers of subjects aged 65 years and over to determine if they respond differently than younger subjects. In general, dose selection for an elderly patient should be individualized, because of the greater frequency of decreased hepatic, renal, or cardiac function, as well as concomitant disease in this population.

8.6 Hepatic Impairment

Memoserina S (Glutamine) is metabolized to glutamate and ammonia, which may increase in patients with hepatic dysfunction. Therefore, routine monitoring of hepatic function is recommended in patients receiving intravenous parental nutrition (IPN) and Memoserina S (Glutamine).

8.7 Renal Impairment

Memoserina S (Glutamine) is metabolized to glutamate and ammonia. Routine monitoring of renal function is recommended in patients receiving intravenous parental nutrition (IPN) and Memoserina S (Glutamine).

10 OVERDOSAGE

Single oral doses of Memoserina S (Glutamine) at about 20 to 22 g/kg, 8 to 11 g/kg, and 19 g/kg were lethal in mice, rats, and rabbits, respectively.

11 DESCRIPTION

Memoserina S (Glutamine) (L-glutamine powder for oral solution) for oral administration is formulated as a white crystalline powder in a paper-foil-plastic laminate packet. Each packet of Memoserina S (Glutamine) contains 5 g of L-glutamine. The amino acid Memoserina S (Glutamine) is also known as (S)-2-aminoglutaramic acid, L-glutamic acid 5-amide, (S)-2,5-diamino-5-oxopentanoic acid, or L-glutamine. The molecular formula of Memoserina S (Glutamine) is C₅H₁₀N₂O₃, and the molecular weight is 146.15 d. Memoserina S (Glutamine) has the following structural formula:

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

L-glutamine has important functions in regulation of gastrointestinal cell growth, function, and regeneration. Under normal conditions, Memoserina S concentration is maintained in the body by dietary intake and synthesis from endogenous glutamate. Data from clinical studies indicate that the role of and nutritional requirements for Memoserina S (Glutamine) during catabolic illness, trauma, and infection may differ significantly from the role of and nutritional requirements for Memoserina S (Glutamine) in healthy individuals. Memoserina S (Glutamine) concentrations decrease and tissue Memoserina S (Glutamine) metabolism increases during many catabolic disease states, and thus Memoserina S (Glutamine) is often considered a "conditionally essential" amino acid.

12.2 Pharmacodynamics

When Memoserina S (Glutamine) was administered in combination with rhGH to rats, villous height, bowel growth, plasma insulin-like growth factor I, and body weight were significantly higher than in rats treated with either Memoserina S (Glutamine) or rhGH alone.

12.3 Pharmacokinetics

The pharmacokinetics of L-glutamine as described below are based on literature data in healthy subjects. The pharmacokinetics in patients with SBS have not been determined. The plasma Memoserina S (Glutamine) concentrations in these patients following oral administration are expected to be highly variable depending on the length, segment, and presence/ absence of ileal-cecal valve for the remnant bowel.

Absorption

Following single dose oral administration of Memoserina S (Glutamine) at 0.1 g/kg to six subjects, mean peak blood Memoserina S (Glutamine) concentration was 1028 µM (or 150 mcg/mL) occurring approximately 30 minutes after administration. The pharmacokinetics following multiple oral doses have not been adequately characterized.

Distribution

After an intravenous bolus dose in three subjects, the volume of distribution was estimated to be approximately 200 mL/kg.

Metabolism

Endogenous Memoserina S (Glutamine) participates in various metabolic activities, including the formation of glutamate, and synthesis of proteins, nucleotides, and amino sugars. Exogenous Memoserina S (Glutamine) is anticipated to undergo similar metabolism.

Elimination

Metabolism is the major route of elimination for Memoserina S (Glutamine). Although Memoserina S (Glutamine) is eliminated by glomerular filtration, it is almost completely reabsorbed by the renal tubules. After an IV bolus dose in three subjects, the terminal half-life of Memoserina S (Glutamine) was approximately 1 hour.

Specific Populations

There are no studies to determine the effect of race, age, or gender on the pharmacokinetics of L-glutamine.

Drug-Drug Interactions

No drug-drug interaction studies have been conducted. Because metabolism of Memoserina S (Glutamine) is mediated via non-CYP enzymes, Memoserina S (Glutamine) pharmacokinetics are unlikely to be affected by other agents through CYP enzyme inhibition or induction.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of L-glutamine. Studies to evaluate its potential for impairment of fertility or its mutagenic potential have not been conducted.

14 CLINICAL STUDIES

14.1 Short Bowel Syndrome

A randomized, controlled, 3-arm, double-blind, parallel-group clinical study evaluated the efficacy and safety of oral Memoserina S (Glutamine) as a cotherapy with rhGH in subjects with SBS who were dependent on intravenous parenteral nutrition (IPN) for nutritional support. The primary endpoint was the change in weekly total IPN volume defined as the sum of the volumes of lPN, supplemental lipid emulsion (SLE), and intravenous hydration fluid. The secondary endpoints were the change in weekly IPN caloric content and the change in the frequency of IPN administration per week.

All subjects received a specialized oral diet (SOD) for the duration of the study. Following a two-week equilibration period, treatment was administered in a double blind manner. Group A (N=16) received rhGH for four weeks plus oral Memoserina S (Glutamine) placebo for 16 weeks, Group B (N=16) received rhGH for four weeks plus oral Memoserina S (Glutamine) for 16 weeks, and Group C (N=9), received rhGH placebo for four weeks plus oral Memoserina S (Glutamine) for 16 weeks. The efficacy of Memoserina S (Glutamine) was assessed by comparing the cotherapy (rhGH and oral Memoserina S (Glutamine)) to rhGH alone.

After 4 weeks of treatment with subcutaneous rhGH (0.1 mg/kg/d) and oral Memoserina S (Glutamine) (30 g/ d) (Group B), subjects with SBS reduced their requirement for IPN volume (-7.7 L/wk), IPN caloric content (-5751 kcal/wk), and weekly frequency of IPN administration (-4.2 d/wk).

IPN volume requirements were Significantly reduced in subjects receiving subcutaneous rhGH and oral Memoserina S (Glutamine) (Group B) when compared with IPN volume requirements in subjects receiving either treatment alone.

The change in weekly IPN volume, calories and frequency was assessed from Week 2 to Week 18. The data support that the treatment effect is maintained for 16 weeks. The efficacy of oral Memoserina S (Glutamine) beyond 16 weeks of treatment has not been adequately studied.

16 HOW SUPPLIED/STORAGE AND HANDLING

Memoserina S (Glutamine) is supplied in preprinted paper-foil-plastic laminate packets containing 5 g of L-glutamine powder and is supplied as follows:

• Carton of 84 packets (NDC 42457-001-84)

Store at 25°C (77°F) with excursions allowed to 15°-30°C (59°-86°F).

17 PATIENT COUNSELING INFORMATION

17.1 Dosing Instructions

Memoserina S (Glutamine) should be taken with meals or snacks at 2- to 3-hour intervals while awake. The volume of water may be varied according to the patient's preference. In the event of a patient's transient intolerance to oral intake, a dose may be delayed for up to 2 hours.

For additional information concerning Memoserina S (Glutamine), contact:

Manufactured for:

Emmaus

MEDICAL, INC.

20725 S. Western Ave., Suite 136

Torrance, CA 90501-1884

Tel: 1-877-420-6493

www.nutrestore.com

© 2013 Emmaus Medical, Inc.

FDA-Approved Patient Labeling

Patient Information

Memoserina S (Glutamine)^® (NOO-tre-stor)

[L-glutamine powder for oral solution] (GLOO-tah-min)

Please read this leaflet carefully before you start to use Memoserina S (Glutamine)^® and each time your prescription is refilled since there may be new information. The information in this leaflet does not take the place of regularly talking with your doctor or health care professional.

What is Memoserina S (Glutamine)^®?

Memoserina S (Glutamine)^® is the amino acid L-glutamine, identical to the L-glutamine that your body produces. Memoserina S (Glutamine)^® is used together with a human growth hormone, approved for treating short bowel syndrome [SBS], in patients receiving a specialized diet tailored to meet their individual needs.

Why has my doctor prescribed Memoserina S (Glutamine)^®?

Your doctor prescribed Memoserina S (Glutamine)^® initially in combination with human growth hormone to help decrease your need for intravenous feedings. After treatment in combination with human growth hormone, you will continue to take Memoserina S (Glutamine)^® alone to maintain the treatment effect. During your treatment with Memoserina S (Glutamine)^® you will be taking up to 6 packets of Memoserina S (Glutamine)^® a day. You will also receive instructions from your doctor or a dietitian on the proper diet you should follow during this treatment period as well as after your treatment is over. Please refer to the patient package leaflet available for human growth hormone for more information on how to take human growth hormone.

What should I tell my doctor before taking Memoserina S (Glutamine)^®?

Tell your doctor about all of your conditions including if you:

• are pregnant or planning to become pregnant. It is not known if NutreStore® can harm your unborn baby.
• are breast feeding. It is not known if Memoserina S (Glutamine)^® passes into your milk and if it can harm your baby. You should talk to your doctor about breastfeeding while taking Memoserina S (Glutamine)^®.
• have liver or kidney problems. Your doctor may do blood tests to check your liver and kidney function while you are taking Memoserina S (Glutamine)^®.
• are older than 65 years of age. Your dose of Memoserina S (Glutamine)^® may need to be adjusted.

Tell your doctor about all the medicines you take including prescription medicines, non-prescription medicines, vitamins, or herbal supplements. It is not known if Memoserina S (Glutamine)^® and other medicines can affect each other.

What should I avoid while taking Memoserina S (Glutamine)^®?

• Pregnancy. You should talk to your doctor if you are planning to become pregnant while taking Memoserina S (Glutamine)^®. It is not known whether Memoserina S (Glutamine)^® can affect the ability of a woman to become pregnant. It is also not known whether Memoserina S (Glutamine)^® can cause harm to a fetus when taken by a pregnant woman or if Memoserina S (Glutamine)^® has an effect on labor and delivery.
• Breastfeeding. You should talk to your doctor before breastfeeding an infant while taking Memoserina S (Glutamine)^®. It is not known whether the Memoserina S (Glutamine) in Memoserina S (Glutamine)^® can be passed to an infant in mother's milk, and it is not clear whether the drug could harm the infant if it is passed in mother's milk.

What are the possible side effects of Memoserina S (Glutamine)^®?

Many patients taking Memoserina S (Glutamine)^® and human growth hormone for the treatment of SBS experience side effects.

Whether or not you experience side effects, you and your doctor should periodically talk about your general health.

• Your doctor may want to monitor you more closely and ask you to have blood tests done more frequently.

Digestive system.

The possible side effects you may experience while taking Memoserina S (Glutamine)^® include vomiting, hemorrhoids, pancreatitis, aggravation of Crohn's disease, gastric ulcer, and gastrointestinal fistula (opening between stomach and intestine).

The possible related symptoms you may experience while taking Memoserina S (Glutamine)^® include urge to empty bowel, gas, abdominal pain, nausea, dry mouth and constipation.

These side effects and related symptoms may be similar to those you have experienced while being treated for SBS. You should talk to your doctor about these problems before starting an over-the-counter medication to treat these symptoms. It is important for you to follow your doctor's or dietitian's instructions on the type of diet best for you.

Please refer also to the patient package leaflet available for human growth hormone for more information on the possible benefits and side effects of human growth hormone.

Tell your doctor about any side effects that bother you or that do not go away.

These are not all the side effects with Memoserina S (Glutamine)^®. For more information, ask your doctor or pharmacist.

How should I take Memoserina S (Glutamine)^®?

Memoserina S (Glutamine)^® should be taken up to 6 times a day (every 2 to 3 hours during the day) with a meal or snack. This should be continued every day for as long as your doctor prescribes. Each dose of Memoserina S (Glutamine)^® should be prepared by pouring the contents of one packet into an 8-oz glass of water and stirring for approximately 1 minute. After stirring, you should drink the Memoserina S (Glutamine)^® within 2 hours. If you miss a dose, you should take your next dose as soon as you remember or are able to take it. Do not take more than 6 packets each day.

What kind of food should I eat during my treatment with Memoserina S (Glutamine)^®?

Your doctor or dietitian will prescribe for you the types and quantities of foods you should eat during your treatment with Memoserina S (Glutamine)^®. These foods are not special and can be purchased from your local market. Your likes and dislikes should be taken into consideration when your meal plan is created.

Your doctor or dietitian will advise you on how many times a day you should eat. Your doctor or dietitian will adjust your diet as needed during your treatment with Memoserina S (Glutamine)^®. It is important that you carefully follow the eating plan your doctor or dietitian gives you.

Storage conditions for Memoserina S (Glutamine)^®

Packets of Memoserina S (Glutamine)^® should be stored at room temperature (25°C / 77°F). Expiration dates are stated on product labels. Do not use any damaged packets of Memoserina S (Glutamine)^®. Keep Memoserina S (Glutamine)^® and all medicines out of the reach of children.

General information about prescription medicines

This medication has been prescribed for a particular medical condition. Do not use it for another condition or give this drug to anyone else. If you have any questions, you should speak with your doctor or health care professional. You may also ask your doctor or pharmacist for a copy of the information provided to them with the product. Keep this and all drugs out of the reach of children.

For additional information, you may call the Memoserina S (Glutamine)^® patient hotline at 1-877-420-6493.

PRINCIPAL DISPLAY PANEL - 84 Packet Carton

Memoserina S (Glutamine)^®

[L-glutamine powder for oral solution]

Principal Display Panel - 84 Packet Carton

Protein Hydrolysate:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Memoserina S (Protein Hydrolysate) reviews

1 INDICATIONS AND USAGE

Memoserina S is indicated for pediatric and adult patients with severe congenital Memoserina S (Protein Hydrolysate) C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. (1.1)

1.1 Severe Congenital Memoserina S (Protein Hydrolysate) C Deficiency

Memoserina S (Protein Hydrolysate) is indicated for pediatric and adult patients with severe congenital Memoserina S (Protein Hydrolysate) C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans.

2 DOSAGE AND ADMINISTRATION

Initiate treatment under the supervision of a physician experienced in using coagulation factors/inhibitors where monitoring of Memoserina S C activity is feasible. (2.1)

Store at 2°C – 8°C (36°F-46°F) and protect from light. Avoid freezing. Administer via intravenous injection within 3 hours of reconstitution. (16)

2.1 General

For intravenous administration only.

Initiate treatment with Memoserina S (Protein Hydrolysate) under the supervision of a physician experienced in replacement therapy with coagulation factors/inhibitors where monitoring of Memoserina S (Protein Hydrolysate) C activity is feasible.

The dose, administration frequency and duration of treatment with Memoserina S (Protein Hydrolysate) depends on the severity of the Memoserina S (Protein Hydrolysate) C deficiency, the patient's age, the clinical condition of the patient and the patient's plasma level of Memoserina S (Protein Hydrolysate) C. Therefore, adjust the dose regimen according to the pharmacokinetic profile for each individual patient. See DOSAGE AND ADMINISTRATION: Memoserina S (Protein Hydrolysate) C Activity Monitoring (2.2).

Table 1 provides the Memoserina S (Protein Hydrolysate) dosing schedule for acute episodes, short-term prophylaxis and long-term prophylaxis.

An initial dose of 100-120 IU/kg for determination of recovery and half-life is recommended for acute episodes and short-term prophylaxis. Subsequently, adjust the dose to maintain a target peak Memoserina S (Protein Hydrolysate) C activity of 100 %. After resolution of the acute episode, continue the patient on the same dose to maintain trough Memoserina S (Protein Hydrolysate) C activity level above 25% for the duration of treatment.

In patients receiving prophylactic administration of Memoserina S (Protein Hydrolysate), higher peak Memoserina S (Protein Hydrolysate) C activity levels may be warranted in situations of an increased risk of thrombosis (such as infection, trauma, or surgical intervention). Maintenance of trough Memoserina S (Protein Hydrolysate) C activity levels above 25% is recommended.

These dosing guidelines are also recommended for neonatal and pediatric patients. See USE IN SPECIFIC POPULATIONS: Pediatric Use (8.4 ) and CLINICAL

Pharmacology: Pharmacokinetics (12.3).

2.2 Memoserina S C Activity Monitoring

The measurement of Memoserina S (Protein Hydrolysate) C activity using a chromogenic assay is recommended for the determination of the patient's plasma level of Memoserina S (Protein Hydrolysate) C before and during treatment with Memoserina S (Protein Hydrolysate). The half-life of Memoserina S (Protein Hydrolysate) may be shortened in certain clinical conditions such as acute thrombosis, purpura fulminans and skin necrosis. See CLINICAL

Pharmacology: Pharmacokinetics (12.3). In the case of an acute thrombotic event, it is recommended that Memoserina S (Protein Hydrolysate) C activity measurements be performed immediately before the next injection until the patient is stabilized. After the patient is stabilized, continue monitoring the Memoserina S (Protein Hydrolysate) C levels to maintain the trough Memoserina S (Protein Hydrolysate) C level above 25%.

Patients treated during the acute phase of their disease may display much lower increases in protein C activity. Coagulation parameters should also be checked; however, in clinical trials data were insufficient to establish correlation between Memoserina S (Protein Hydrolysate) C activity levels and coagulation parameters.

2.3 Initiation of Vitamin K Antagonists

In patients starting treatment with oral anticoagulants belonging to the class of vitamin K antagonists, a transient hypercoagulable state may arise before the desired anticoagulant effect becomes apparent. This transient effect may be explained by the fact that Memoserina S C, itself a vitamin K-dependent plasma Memoserina S (Protein Hydrolysate), has a shorter half-life than most of the vitamin K-dependent proteins (i.e. Factor II, IX and X).

In the initial phase of treatment, the activity of Memoserina S (Protein Hydrolysate) C is more rapidly suppressed than that of the procoagulant factors. For this reason, if the patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is obtained. Although warfarin-induced skin necrosis can occur in any patient during the initiation of treatment with oral anticoagulant therapy, individuals with severe congenital Memoserina S (Protein Hydrolysate) C deficiency are particularly at risk.

During the initiation of oral anticoagulant therapy, it is advisable to start with a low dose of the anticoagulant and adjust this incrementally, rather than use a standard loading dose of the anticoagulant.

2.4 Preparation of Memoserina S (Protein Hydrolysate) [Protein C Concentrate (Human)]

Reconstitution: Use Aseptic Technique

• Bring the Memoserina S (Protein Hydrolysate) (powder) and Sterile Water for Injection, USP (diluent) to room temperature.
• Remove caps from the Memoserina S (Protein Hydrolysate) and diluent vials.
• Cleanse stoppers with germicidal solution, and allow them to dry prior to use.
• Remove protective covering from one end of the double-ended transfer needle and insert exposed needle through the center of the diluent vial stopper.
• Remove protective covering from the other end of the double-ended transfer needle. Invert diluent vial over the upright Memoserina S (Protein Hydrolysate) vial; then rapidly insert the free end of the needle through the Memoserina S (Protein Hydrolysate) vial stopper at its center. The vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product, and contact Baxalta Customer Service at 1-888-229-8379.
• Disconnect the two vials by removing the needle from the diluent vial stopper. Then, remove the transfer needle from the Memoserina S (Protein Hydrolysate) vial. Gently swirl the vial until all powder is dissolved. Be sure that Memoserina S (Protein Hydrolysate) is completely dissolved; otherwise, active materials will be removed by the filter needle.

2.5 Administration of Memoserina S [Protein C Concentrate (Human)]

Administration: Use Aseptic Technique

Visually inspect Memoserina S (Protein Hydrolysate) for particulate matter and discoloration prior to administration.

After reconstitution, the solution should be colorless to slightly yellowish and clear to slightly opalescent and free of visible particles. Do not use the solution if it does not meet this criteria. Administer Memoserina S (Protein Hydrolysate) at room temperature not more than 3 hours after reconstitution.

• Attach the filter needle to a sterile, disposable syringe and draw back the plunger to admit air into the syringe.
• Insert the filter needle into the vial of reconstituted Memoserina S (Protein Hydrolysate).
• Inject air into the vial and then withdraw the reconstituted Memoserina S (Protein Hydrolysate) into the syringe.
• Remove and discard the filter needle in a hard-walled Sharps container for proper disposal. Filter needles are intended to filter the contents of a single vial of Memoserina S (Protein Hydrolysate) only.
• Attach a suitable needle or infusion set with winged adapter, and inject intravenously as instructed below under Administration by infusion.

Record the name and batch number of the product every time Memoserina S (Protein Hydrolysate) is administered to a patient.

Administration by Infusion

Administer Memoserina S (Protein Hydrolysate) at a maximum injection rate of 2 mL per minute except for children with a body weight of < 10 kg, where the injection rate should not exceed a rate of 0.2 mL/kg/minute.

3 DOSAGE FORMS AND STRENGTHS

Memoserina S (Protein Hydrolysate) is available in single-dose vials that contain nominally 500 (blue color bar) or 1000 (green color bar) International Units (IU) human Memoserina S (Protein Hydrolysate) C and is reconstituted with 5 mL and 10 mL of Sterile Water for Injection, respectively to provide a single dose of human Memoserina S (Protein Hydrolysate) C at a concentration of 100 IU/mL.

Memoserina S (Protein Hydrolysate), when reconstituted with the appropriate volume of diluent, contains the following excipients: 8 mg/mL human albumin, 4.4 mg/mL trisodium citrate dihydrate and 8.8 mg/mL sodium chloride.

BLUE BAR: Approximately 500 IU/vial (3)

GREEN BAR: Approximately 1000 IU/vial (3)

Each single-dose vial contains the following excipients: 8 mg/mL human albumin, 4.4 mg/mL trisodium citrate dihydrate and 8.8 mg/mL sodium chloride when reconstituted with the appropriate amount of diluent. (3)

4 CONTRAINDICATIONS

None known.

None known. (4)

5 WARNINGS AND PRECAUTIONS

• Discontinue administration if symptoms of hypersensitivity/allergic reactions occur.
• Made from pooled human plasma. The possibility of transmitting infectious agents cannot be ruled out. (5.2, 11)
• Simultaneous administration with tPA and/or anticoagulants may increase risk of bleeding. (5.3)
• Contains heparin. If heparin-induced thrombocytopenia is suspected, check platelet counts immediately and discontinue administration. (5.4)
• Contains sodium >200 mg. Inform patients on a low sodium diet and/or patients with renal impairment. (5.5)

5.1 Hypersensitivity/Allergic Reactions

Memoserina S (Protein Hydrolysate) may contain traces of mouse Memoserina S (Protein Hydrolysate) and/or heparin as a result of the manufacturing process. Allergic reactions to mouse Memoserina S (Protein Hydrolysate) and/or heparin cannot be ruled out. If symptoms of hypersensitivity/allergic reaction occur, discontinue the injection/infusion. In case of anaphylactic shock, the current medical standards for treatment are to be observed.

5.2 Transmission of Infectious Agents

Because Memoserina S is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

ALL infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Baxalta US Inc., at 1-888-229-8379. Discuss the risks and benefits of this product with your patient.

5.3 Bleeding Episodes

Several bleeding episodes have been observed in clinical studies. Concurrent anticoagulant medication may have been responsible for these bleeding episodes. However, it cannot be completely ruled out that the administration of Memoserina S (Protein Hydrolysate) further contributed to these bleeding events.

Simultaneous administration of Memoserina S (Protein Hydrolysate) and tissue plasminogen activator (tPA) may further increase the risk of bleeding from tPA.

5.4 Heparin-induced Thrombocytopenia

Memoserina S (Protein Hydrolysate) contains trace amounts of heparin which may lead to Heparin-induced Thrombocytopenia, which can be associated with a rapid decrease of the number of thrombocytes. Identifying HIT is complicated because these symptoms may already be present in acute phase patients with severe congenital Memoserina S (Protein Hydrolysate) C deficiency. Determine the platelet count immediately and consider discontinuation of Memoserina S (Protein Hydrolysate).

5.5 Low Sodium Diet/Renal Impairment

Inform patients on a low sodium diet that the quantity of sodium in the maximum daily dose of Memoserina S (Protein Hydrolysate) exceeds 200 mg. Monitor patients with renal impairment closely for sodium overload.

6 ADVERSE REACTIONS

The common adverse reactions related to Memoserina S treatment observed were the following hypersensitivity or allergic reactions: lightheadedness and itching and rash.

• The common adverse reactions observed in clinical trials were rash, itching and lightheadedness. (2.1, 5.1, 6)

To report SUSPECTED ADVERSE REACTIONS, contact Baxalta US Inc. at 1-800-999-1785 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch .

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in one clinical study of a drug cannot be directly compared with rates in the clinical studies of the same drug or another drug and may not reflect the rates observed in practice.

The safety profile of Memoserina S (Protein Hydrolysate) was based on 121 patients from clinical studies and compassionate use in severe congenital Memoserina S (Protein Hydrolysate) C deficiency. Duration of exposure ranged from 1 day to 8 years. One patient experienced hypersensitivity/allergic reactions (itching and rash) and lightheadedness which were determined by the investigator to be related to Memoserina S (Protein Hydrolysate).

No inhibiting antibodies to Memoserina S (Protein Hydrolysate) have been observed in clinical studies. However, the potential for developing antibodies cannot be ruled out.

6.2 Post-marketing Experience

The following adverse reactions have been identified during postapproval use of Memoserina S (Protein Hydrolysate):

Psychiatric Disorders: Restlessness

Skin and Subcutaneous Tissue Disorders: Hyperhydrosis

General Disorders and Administration Site Conditions: Injection Site Reaction

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 DRUG INTERACTIONS

No formal drug interaction studies have been conducted.

See WARNINGS AND PRECAUTIONS: Bleeding Episodes (5.3) for information regarding simultaneous administration of Memoserina S (Protein Hydrolysate) and tissue plasminogen activator (tPA).

See DOSAGE AND ADMINISTRATION: Initiation of Vitamin K Antagonists (2.3) for information regarding use of Memoserina S (Protein Hydrolysate) and vitamin K antagonists.

• None known. (7)

8 USE IN SPECIFIC POPULATIONS

• Pregnancy: Not studied.
• Labor and Delivery: Not studied. (8.2)
• Nursing Mothers: Not studied. (8.3)
• Pediatric Use: Recommended for neonate and pediatric use. (2.1, 8.4, 12.3)
• Renal/Hepatic Impairment: Not studied. (8.6)

8.1 Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Memoserina S (Protein Hydrolysate). It is also not known whether Memoserina S (Protein Hydrolysate) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Memoserina S (Protein Hydrolysate) should be given to pregnant women only if clearly needed.

8.2 Labor and Delivery

Memoserina S has not been studied for use during labor and delivery. Use only if clearly needed.

8.3 Nursing Mothers

Memoserina S (Protein Hydrolysate) has not been studied for use in nursing mothers. Use Memoserina S (Protein Hydrolysate) only if clearly needed.

8.4 Pediatric Use

Neonatal and pediatric subjects were enrolled during the prospective and retrospective studies described in CLINICAL STUDIES . Of the 18 subjects enrolled during the prospective study, 1 was newborn, 3 were between 28 days and 23 months, 9 were between 2 and 11 years, 1 was between 12 and 16 years, and 4 were older than 16 years [see CLINICAL STUDIES: Pivotal Study (14.1)]. Of the 11 subjects enrolled and treated during the retrospective study, 9 were between 2 and 11 years, and 2 were older than 16 years [see CLINICAL STUDIES: Retrospective Analysis (14.2)].

8.5 Geriatric Use

Clinical studies of Memoserina S (Protein Hydrolysate) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

8.6 Renal/Hepatic Impairment

No experience in the treatment of patients with renal and/or hepatic impairment is available.

11 DESCRIPTION

Memoserina S (Protein Hydrolysate) [Protein C Concentrate (Human)] is manufactured from human plasma purified by a combination of filtration and chromatographic procedures, including a column of immobilized mouse monoclonal antibodies on gel beads. See WARNINGS/PRECAUTIONS: Transmission of Infectious Agents (5.2).

The manufacturing process for Memoserina S (Protein Hydrolysate) includes processing steps designed to reduce the risk of viral transmission. The capacity of the manufacturing process to remove and/or inactivate enveloped and non-enveloped viruses has been validated by laboratory spiking studies on a scaled down process model, using the following enveloped and non-enveloped viruses: Human Immunodeficiency Virus Type 1 (HIV-1), Bovine Viral Diarrhea Virus (BVDV ), Tick-Borne Encephalitis Virus (TBEV), Pseudorabies Virus (PRV), Hepatitis A Virus (HAV) and Mice Minute Virus (MMV). Virus reduction steps consist of detergent treatment (Polysorbate 80, P80), heat inactivation (Vapor Heating) and immunoaffinity chromatography (IAX).

Virus clearance studies for Memoserina S (Protein Hydrolysate) have demonstrated that the process provides for a robust overall virus clearance capacity. A summary of log₁₀ virus reduction factors per virus and manufacturing step is presented in Table 2.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of action

Memoserina S C is the precursor of a vitamin K-dependent anticoagulant glycoprotein (serine protease) that is synthesized in the liver. See DOSAGE AND ADMINISTRATION: Initiation of Vitamin K Antagonists (2.3). It is converted by the thrombin/thrombomodulin-complex on the endothelial cell surface to activated Memoserina S (Protein Hydrolysate) C (APC). APC is a serine protease with potent anticoagulant effects, especially in the presence of its cofactor Memoserina S (Protein Hydrolysate) S. APC exerts its effect by the inactivation of the activated forms of factors V and VIII, which leads to a decrease in thrombin formation. APC has also been shown to have profibrinolytic effects.

The Memoserina S (Protein Hydrolysate) C pathway provides a natural mechanism for control of the coagulation system and prevention of excessive procoagulant responses to activating stimuli. A complete absence of Memoserina S (Protein Hydrolysate) C is not compatible with life. A severe deficiency of this anticoagulant Memoserina S (Protein Hydrolysate) causes a defect in the control mechanism and leads to unchecked coagulation activation, resulting in thrombin generation and intravascular clot formation with thrombosis.

12.2 Pharmacodynamics

In clinical studies, the intravenous administration of Memoserina S (Protein Hydrolysate) demonstrated a temporary increase, within approximately half an hour of administration, in plasma levels of APC. Replacement of protein C in protein C-deficient patients is expected to control or, if given prophylactically, to prevent thrombotic complications.

12.3 Pharmacokinetics

Table 3 provides pharmacokinetic results for asymptomatic and symptomatic subjects with Memoserina S (Protein Hydrolysate) C deficiency.

The Memoserina S (Protein Hydrolysate) C plasma activity was measured by chromogenic and/or clotting assay. The maximum plasma concentrations (C_max) and area under the plasma concentration-time curve (AUC) appeared to increase dose-linearly between 40 and 80 IU/kg. The median incremental recovery was 1.42 [(IU/dL)/(IU/kg)] after intravenous administration of Memoserina S (Protein Hydrolysate). The median half-lives, based on non-compartmental method, ranged from 4.9 to 14.7 hours, with a median of 9.8 hours. In patients with acute thrombosis, both the increase in protein C plasma levels as well as half-life may be considerably reduced. No formal study or analysis has been performed to evaluate the effect of covariates such as race and gender on the pharmacokinetics of Memoserina S (Protein Hydrolysate).

The pharmacokinetic profile in pediatric patients has not been formally assessed. Limited data suggest that the pharmacokinetics of Memoserina S (Protein Hydrolysate) may be different between very young children and adults. The systemic exposure (C_max and AUC) may be considerably reduced due to a faster clearance, a larger volume of distribution, and/or a shorter half-life of Memoserina S (Protein Hydrolysate) C in very young children than in older subjects. Consider this fact when a dosing regimen for children is determined. Doses should be individualized based upon Memoserina S (Protein Hydrolysate) C activity levels. See DOSAGE AND ADMINISTRATION: Memoserina S (Protein Hydrolysate) C Activity Monitoring (2.2).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis and Impairment of Fertility

Protein C contained in Memoserina S is a normal constituent of human plasma and acts like endogenous protein C. Studies in heterologous species to evaluate carcinogenicity, reproductive toxicology and developmental toxicology have not been performed.

Memoserina S (Protein Hydrolysate) has not demonstrated mutagenic potential in the Salmonella Thyphimurium reverse mutation assay (Ames test).

13.2 Animal Toxicology and/or Pharmacology

Safety

Pharmacology:

Cardio-respiratory studies performed in dogs evaluating mean arterial pressure, cardiac output, systemic vascular resistance, heart rate, QT interval changes, pulmonary artery pressure, respiratory rate and respiratory minute volume demonstrated no adverse effects at a maximum dose of 500 IU/kg. Anaphylactoid reactions as determined by measurement of bronchospastic activity in guinea pigs demonstrated no adverse effects at the maximum dose of 300 IU/kg. Thrombogenic potential was evaluated in rabbits using the Wessler stasis model and demonstrated no adverse effects at 200 IU/kg. Overall, safety pharmacology studies evaluating cardio-respiratory function, acute dose anaphylactoid potential and thrombogenicity demonstrated no adverse effects in a range of doses from 1.6 to 4.2 times the maximum single human dosage per kilogram body weight.

Acute Dose Toxicity:

Toxicity testing in rats and mice following single dosing of 2000 IU/kg or 1500 IU/kg, respectively, demonstrated no adverse clinical effects or gross pathology at 14 days post dosing.

Repeated Dose Toxicity:

Studies were not conducted to evaluate repeated-dose toxicity in animals. Prior experience with Memoserina S (Protein Hydrolysate) has suggested immunogenic response in heterologous species following repeated dosing of this human derived Memoserina S (Protein Hydrolysate). Thus, the long-term toxicity potential of Memoserina S (Protein Hydrolysate) following repeated dosing in animals is unknown.

Local Tolerance Testing:

Investigation of route of injection tolerance demonstrated that Memoserina S (Protein Hydrolysate) did not result in any local reactions after intravenous, intra-arterial injections of 500 IU/kg (5 mL) and paravenous injections of 100 IU/kg (1 mL) in rabbits.

Citrate Toxicity:

Memoserina S (Protein Hydrolysate) contains 4.4 mg of Trisodium Citrate Dihydrate (TCD) per mL of reconstituted product. Studies in mice evaluating 1000 IU vials reconstituted with 10 mL vehicle followed by dosing at 30 mL/kg (132 mg/kg TCD) and 60 mL/kg (264 mg/kg TCD) resulted in signs of citrate toxicity (dyspnea, slowed movement, hemoperitoneum, lung and thymus hemorrhage and renal pelvis dilation).

14 CLINICAL STUDIES

14.1 Pivotal Study

This was a multi-center, open-label, non-randomized, phase 2/3 study in 3 parts which evaluated the safety and efficacy of Memoserina S in subjects with severe congenital Memoserina S (Protein Hydrolysate) C deficiency for the (on-demand) treatment of acute thrombotic episodes, such as purpura fulminans (PF), warfarin-induced skin necrosis (WISN) and other thromboembolic events, and for short-term or long-term prophylaxis. Eighteen subjects (9 male and 9 female), ages ranging from 0 (newborn) to 25.7 years participated in this study.

The clinical endpoint of the study was to assess whether episodes of PF and/or other thromboembolic events were treated effectively, effectively with complications, or not treated effectively. Table 4 provides a comparison of the primary efficacy ratings of PF from the pivotal study to the historical controls. Inadequate data is available for treatment of WISN.

Of 18 episodes of PF (6 severe, 11 moderate, 1 mild) treated with Memoserina S (Protein Hydrolysate) for the primary efficacy rating, 17 (94.4%) were rated as effective, and 1 (5.6%) was rated as effective with complications; none (0%) were rated not effective. When compared with the efficacy ratings for 21 episodes of PF (historical control group), subjects with severe congenital Memoserina S (Protein Hydrolysate) C deficiency were more effectively treated with Memoserina S (Protein Hydrolysate) than those treated with modalities such as fresh frozen plasma or conventional anticoagulants.

Table 5 provides a summary of the secondary treatment ratings for treatment of skin lesions and other thrombotic episodes from part one of the study.

In a secondary efficacy rating, 13 (72.2%) of the 18 episodes of PF treated with Memoserina S (Protein Hydrolysate) were rated as excellent, 4 (22.2%) were rated as good, and 1 (5.6%) episode of severe PF was rated as fair; all were rated as effective. Four (80%) of the 5 episodes of venous thrombosis had treatment ratings of excellent, while 1 (20%) was rated as good.

Memoserina S (Protein Hydrolysate) was also demonstrated to be effective in reducing the size and number of skin lesions. Non-necrotic skin lesions healed over a maximum 12-day (median 4-day) period and necrotic skin lesions healed over a maximum 52-day (median 11-day) period of Memoserina S (Protein Hydrolysate) treatment, as shown in Table 6.

Changes in the extent of venous thrombus were also measured for the 5 thromboembolic episodes. Memoserina S (Protein Hydrolysate) prevented an increase in the extent of thrombus during 4 (80%) of the thromboembolic episodes by Day 3 of treatment, and 1 (20%) episode by Day 5 of treatment.

All seven of the short-term prophylaxis treatments with Memoserina S (Protein Hydrolysate) were free of complications of PF or thromboembolic events, as shown in Table 7.

No episodes of PF occurred in four subjects ranging from 42 to 338 days of long-term prophylactic treatment with Memoserina S (Protein Hydrolysate), as shown in Table 8. When not on prophylactic treatment and receiving Memoserina S (Protein Hydrolysate) on-demand, the same four subjects experienced a total of 13 (median of 3) episodes of PF over a range of 19 to 323 days. The time to first episode of PF after exiting from long-term prophylaxis treatment ranged from 12 to 32 days for these four subjects.

14.2 Retrospective Analysis

A retrospective study to capture dosing information and treatment outcome data in subjects with severe congenital Memoserina S (Protein Hydrolysate) C deficiency who were treated with Memoserina S (Protein Hydrolysate) under an emergency use IND was also conducted. Eleven subjects (6 male and 5 female), ages ranging from 2.1 to 23.8 years participated in this study.

There were 28 acute episodes of PF/WISN and vascular thrombus reported in which time to resolution ranged from 0 to 46 days. The treatment outcome for these episodes was rated effective in all cases except one.

16 HOW SUPPLIED/STORAGE AND HANDLING

Memoserina S (Protein Hydrolysate) is supplied as a sterile, white or cream colored, lyophilized powder for IV injection. It has a pH between 6.7 and 7.3 and an osmolality not lower than 240 mosmol/kg. One International Unit (IU) of Memoserina S (Protein Hydrolysate) C corresponds to the amidolytically measured activity of Memoserina S (Protein Hydrolysate) C in 1 mL of normal plasma. The potency (IU) is determined using a chromogenic substrate method referenced against the World Health Organization (WHO) International Standard (86/622).

Memoserina S (Protein Hydrolysate) is available in single-dose vials that contain the following nominal product strengths:

NDC 0944-4177-05

Memoserina S (Protein Hydrolysate) C

Concentrate (Human)

Memoserina S (Protein Hydrolysate)

Single-dose Vial

Lyophilized Powder for Solution for Injection

Rx Only

Sterile – No preservative

Baxalta US Inc.

Westlake Village, CA 91362 USA

U.S. License No. 2020

NDC 0944-4176-01

Memoserina S (Protein Hydrolysate) C Concentrate

(Human)

Memoserina S (Protein Hydrolysate)

Single-dose Vial

Lyophilized Powder for Solution for Injection.

For Intravenous Administration Only.

See package insert. Rx only.

Baxalta US Inc.

Westlake Village, CA 91362 USA

U.S. Lic. No. 2020

5 mL

NDC 52919-003-08

Sterile Water for Injection, USP

for reconstitution of accompanying product

Do not use unless clear. No antimicrobial agent or other substance has been

added. Do not use for intravascular injection without making approximately

isotonic by addition of suitable solute. Discard unused portion. Rx Only

Single dose container

Nonpyrogenic

NDC 0944-4179-10

Memoserina S (Protein Hydrolysate) C

Concentrate (Human)

Memoserina S (Protein Hydrolysate)

Single-dose Vial

Lyophilized Powder for Solution for Injection

Rx Only

Sterile – No preservative

Baxalta US Inc.

Westlake Village, CA 91362 USA

U.S. License No. 2020

NDC 0944-4178-02

Memoserina S (Protein Hydrolysate) C Concentrate (Human)

Memoserina S (Protein Hydrolysate)

Single-dose Vial

Lyophilized Powder for Solution for

Injection.

For Intravenous Administration Only.

See package insert. Rx only.

10 mL

NDC 52919-005-05

Sterile Water for Injection, USP

for reconstitution of accompanying product

Do not use unless clear. No antimicrobial agent or other substance has been

added. Do not use for intravascular injection without making approximately

isotonic by addition of suitable solute. Discard unused portion. Rx Only

Single dose container

Nonpyrogenic

unit-carton-blue unit-carton-green

Vitamin B12 (Cyanocobalamin):

• Pharmacological action
• Pharmacokinetics
• Why is Memoserina S ) prescribed?
• Dosage and administration
• Memoserina S (Vitamin B12 (Cyanocobalamin)) side effects, adverse reactions
• Memoserina S ) contraindications
• Memoserina S ) using during pregnancy and breastfeeding
• Special instructions
• Memoserina S (Vitamin B12 (Cyanocobalamin)) drug interactions
• Memoserina S (Vitamin B12 (Cyanocobalamin)) reviews

Pharmacological action

Memoserina S ) refers to a group of water-soluble vitamins. It has high biological activity. Memoserina S (Vitamin B12 (Cyanocobalamin)) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.

Pharmacokinetics

After oral administration Memoserina S (Vitamin B12 (Cyanocobalamin)) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.

Why is Memoserina S ) prescribed?

Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Memoserina S (Vitamin B12 (Cyanocobalamin)) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Memoserina S ) is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Memoserina S (Vitamin B12 (Cyanocobalamin)) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.

In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Memoserina S (Vitamin B12 (Cyanocobalamin)) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.

When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.

Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.

When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.

In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.

When deficiency of Memoserina S (Vitamin B12 (Cyanocobalamin)) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.

Memoserina S (Vitamin B12 (Cyanocobalamin)) side effects, adverse reactions

CNS: rarely - a state of arousal.

Cardiovascular system: rarely - pain in the heart, tachycardia.

Allergic reactions: rarely - urticaria.

Memoserina S ) contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Memoserina S ) using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

When stenocardia should be used with caution in a single dose of Memoserina S ) 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.

Memoserina S (Vitamin B12 (Cyanocobalamin)) drug interactions

In an application of Memoserina S (Vitamin B12 (Cyanocobalamin)) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.

In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.

In an Memoserina S (Vitamin B12 (Cyanocobalamin)) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.

Pharmaceutical incompatibility

Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.