|
|||
DRUGS & SUPPLEMENTS
|
What are the side effects you encounter while taking this medicine? |
L-Lysine:
Indication: Supplemental Beth-P (L-Lysine) has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.
Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.
Protein Hydrolysate:
Beth-P is indicated for pediatric and adult patients with severe congenital Beth-P (Protein Hydrolysate) C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. (1.1)
Beth-P (Protein Hydrolysate) is indicated for pediatric and adult patients with severe congenital Beth-P (Protein Hydrolysate) C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans.
Initiate treatment under the supervision of a physician experienced in using coagulation factors/inhibitors where monitoring of Beth-P C activity is feasible. (2.1)
Beth-P (Protein Hydrolysate) Dosing Schedule for Acute Episodes, Short-term Prophyaxis and Long-term Prophylaxis | |||
Initial Dose | Subsequent # Doses | Maintenance Dose | |
Acute Episodes, Short-term Prophyaxis | 100-120 IU/kg | 60-80 IU/kg Q 6 hours | 45-60 IU/kg Q 6 or Q 12 hours |
Long-term Prophylaxis | NA | NA | 45-60 IU/kg Q 12 hours |
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)
For intravenous administration only.
Initiate treatment with Beth-P (Protein Hydrolysate) under the supervision of a physician experienced in replacement therapy with coagulation factors/inhibitors where monitoring of Beth-P (Protein Hydrolysate) C activity is feasible.
The dose, administration frequency and duration of treatment with Beth-P (Protein Hydrolysate) depends on the severity of the Beth-P (Protein Hydrolysate) C deficiency, the patient's age, the clinical condition of the patient and the patient's plasma level of Beth-P (Protein Hydrolysate) C. Therefore, adjust the dose regimen according to the pharmacokinetic profile for each individual patient. See DOSAGE AND ADMINISTRATION: Beth-P (Protein Hydrolysate) C Activity Monitoring (2.2).
Table 1 provides the Beth-P (Protein Hydrolysate) dosing schedule for acute episodes, short-term prophylaxis and long-term prophylaxis.
NA = Not applicable; Q = every. | |||
Initial Dose | Subsequent 3 Doses | Maintenance Dose | |
Acute Episode / Short-term Prophylaxis | 100-120 IU/kg | 60 - 80 IU/kg Q 6 hours | 45 - 60 IU/kg Q 6 or 12 hours |
Long-term Prophylaxis | NA | NA | 45 - 60 IU/kg Q 12 hours |
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 Beth-P (Protein Hydrolysate) C activity of 100 %. After resolution of the acute episode, continue the patient on the same dose to maintain trough Beth-P (Protein Hydrolysate) C activity level above 25% for the duration of treatment.
In patients receiving prophylactic administration of Beth-P (Protein Hydrolysate), higher peak Beth-P (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 Beth-P (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).
The measurement of Beth-P (Protein Hydrolysate) C activity using a chromogenic assay is recommended for the determination of the patient's plasma level of Beth-P (Protein Hydrolysate) C before and during treatment with Beth-P (Protein Hydrolysate). The half-life of Beth-P (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 Beth-P (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 Beth-P (Protein Hydrolysate) C levels to maintain the trough Beth-P (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 Beth-P (Protein Hydrolysate) C activity levels and coagulation parameters.
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 Beth-P C, itself a vitamin K-dependent plasma Beth-P (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 Beth-P (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 Beth-P (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.
Reconstitution: Use Aseptic Technique
Administration: Use Aseptic Technique
Visually inspect Beth-P (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 Beth-P (Protein Hydrolysate) at room temperature not more than 3 hours after reconstitution.
Record the name and batch number of the product every time Beth-P (Protein Hydrolysate) is administered to a patient.
Administration by Infusion
Administer Beth-P (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.
Beth-P (Protein Hydrolysate) is available in single-dose vials that contain nominally 500 (blue color bar) or 1000 (green color bar) International Units (IU) human Beth-P (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 Beth-P (Protein Hydrolysate) C at a concentration of 100 IU/mL.
Beth-P (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)
None known.
None known. (4)
Beth-P (Protein Hydrolysate) may contain traces of mouse Beth-P (Protein Hydrolysate) and/or heparin as a result of the manufacturing process. Allergic reactions to mouse Beth-P (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.
Because Beth-P 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.
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 Beth-P (Protein Hydrolysate) further contributed to these bleeding events.
Simultaneous administration of Beth-P (Protein Hydrolysate) and tissue plasminogen activator (tPA) may further increase the risk of bleeding from tPA.
Beth-P (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 Beth-P (Protein Hydrolysate) C deficiency. Determine the platelet count immediately and consider discontinuation of Beth-P (Protein Hydrolysate).
Inform patients on a low sodium diet that the quantity of sodium in the maximum daily dose of Beth-P (Protein Hydrolysate) exceeds 200 mg. Monitor patients with renal impairment closely for sodium overload.
The common adverse reactions related to Beth-P treatment observed were the following hypersensitivity or allergic reactions: lightheadedness and itching and rash.
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 .
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 Beth-P (Protein Hydrolysate) was based on 121 patients from clinical studies and compassionate use in severe congenital Beth-P (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 Beth-P (Protein Hydrolysate).
No inhibiting antibodies to Beth-P (Protein Hydrolysate) have been observed in clinical studies. However, the potential for developing antibodies cannot be ruled out.
The following adverse reactions have been identified during postapproval use of Beth-P (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.
No formal drug interaction studies have been conducted.
See WARNINGS AND PRECAUTIONS: Bleeding Episodes (5.3) for information regarding simultaneous administration of Beth-P (Protein Hydrolysate) and tissue plasminogen activator (tPA).
See DOSAGE AND ADMINISTRATION: Initiation of Vitamin K Antagonists (2.3) for information regarding use of Beth-P (Protein Hydrolysate) and vitamin K antagonists.
Pregnancy Category C. Animal reproduction studies have not been conducted with Beth-P (Protein Hydrolysate). It is also not known whether Beth-P (Protein Hydrolysate) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Beth-P (Protein Hydrolysate) should be given to pregnant women only if clearly needed.
Beth-P has not been studied for use during labor and delivery. Use only if clearly needed.
Beth-P (Protein Hydrolysate) has not been studied for use in nursing mothers. Use Beth-P (Protein Hydrolysate) only if clearly needed.
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)].
Clinical studies of Beth-P (Protein Hydrolysate) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
No experience in the treatment of patients with renal and/or hepatic impairment is available.
Beth-P (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 Beth-P (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 Beth-P (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.
Abbreviations: IEX, Ion Exchange Chromatography; IAX, Immunoaffinity Chromatography; HIV-1, Human Immunodeficiency Virus Type I; TBEV, Tick-Borne Encephalitis Virus (model for hepatitis C virus); BVDV, Bovine Viral Diarrhea Virus (model virus for HCV and other small, enveloped RNA viruses); PRV, Pseudorabies Virus (model virus for enveloped DNA viruses, e.g. HBV, Hepatitis B Virus); HAV, Hepatitis A Virus; MMV, Mice Minute Virus (model for Human Parvovirus B19 and for non enveloped viruses); n.d., not done. | ||||||
Manufact-uring Step | HIV-1 | HCV Model Viruses | PRV | HAV | MMV | |
BVDV | TBEV | |||||
P80 Treatment | >5.1 | >4.7 | n.d. | 2.5 | >3.8 | 1.4 |
IAX | 5.7 | n.d. | 4.8 | 5.4 | 3.1 | 3.6 |
Vapor Heating | 4.6 | >5.9 | n.d. | 5.9 | >4.2 | 1.2 |
Beth-P 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 Beth-P (Protein Hydrolysate) C (APC). APC is a serine protease with potent anticoagulant effects, especially in the presence of its cofactor Beth-P (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 Beth-P (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 Beth-P (Protein Hydrolysate) C is not compatible with life. A severe deficiency of this anticoagulant Beth-P (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.
In clinical studies, the intravenous administration of Beth-P (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.
Table 3 provides pharmacokinetic results for asymptomatic and symptomatic subjects with Beth-P (Protein Hydrolysate) C deficiency.
PK parameter | N | Median | 95% CI for median | Min | Max |
Cmax [IU/dL] | 21 | 110 | 106 to 127 | 40 | 141 |
Tmax [h] | 21 | 0.50 | 0.50 to 1.05 | 0.17 | 1.33 |
Incremental recovery [(IU/dL)/(IU/kg)] | 21 | 1.42 | 1.32 to 1.59 | 0.50 | 1.76 |
Initial half-life [h] | 21 | 7.8 | 5.4 to 9.3 | 3.0 | 36.1 |
Terminal half-life [h] | 21 | 9.9 | 7.0 to 12.4 | 4.4 | 15.8 |
Half-life by the non-compartmental approach [h] | 21 | 9.8 | 7.1 to 11.6 | 4.9 | 14.7 |
AUC0-Infinity [IU*h/dL] | 21 | 1500 | 1289 to 1897 | 344 | 2437 |
MRT [h] | 21 | 14.1 | 10.3 to 16.7 | 7.1 | 21.3 |
Clearance [dL/kg/h] | 21 | 0.0533 | 0.0428 to 0.0792 | 0.0328 | 0.2324 |
Volume of distribution at steady state [dL/kg] | 21 | 0.74 | 0.70 to 0.89 | 0.44 | 1.65 |
Cmax = Maximum concentration after infusion; T max = Time at maximum concentration; AUC 0-Infinity = Area under the curve from 0 to infinity; MRT = Mean residence time; and Incremental recovery = Maximum increase in Beth-P (Protein Hydrolysate) C concentration following infusion divided by dose |
The Beth-P (Protein Hydrolysate) C plasma activity was measured by chromogenic and/or clotting assay. The maximum plasma concentrations (Cmax) 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 Beth-P (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 Beth-P (Protein Hydrolysate).
The pharmacokinetic profile in pediatric patients has not been formally assessed. Limited data suggest that the pharmacokinetics of Beth-P (Protein Hydrolysate) may be different between very young children and adults. The systemic exposure (Cmax and AUC) may be considerably reduced due to a faster clearance, a larger volume of distribution, and/or a shorter half-life of Beth-P (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 Beth-P (Protein Hydrolysate) C activity levels. See DOSAGE AND ADMINISTRATION: Beth-P (Protein Hydrolysate) C Activity Monitoring (2.2).
Protein C contained in Beth-P 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.
Beth-P (Protein Hydrolysate) has not demonstrated mutagenic potential in the Salmonella Thyphimurium reverse mutation assay (Ames test).
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 Beth-P (Protein Hydrolysate) has suggested immunogenic response in heterologous species following repeated dosing of this human derived Beth-P (Protein Hydrolysate). Thus, the long-term toxicity potential of Beth-P (Protein Hydrolysate) following repeated dosing in animals is unknown.
Local Tolerance Testing:
Investigation of route of injection tolerance demonstrated that Beth-P (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:
Beth-P (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).
This was a multi-center, open-label, non-randomized, phase 2/3 study in 3 parts which evaluated the safety and efficacy of Beth-P in subjects with severe congenital Beth-P (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.
Beth-P (Protein Hydrolysate) C Concentrate (Human) | Historical Controls | ||||
Episode Type | Primary Efficacy Rating | N | % | N | % |
Purpura Fulminans | Effective | 17 | 94.4 | 11 | 52.4 |
Effective with Complication | 1 | 5.6 | 7 | 33.3 | |
Not Effective | 0 | 0.0 | 3 | 14.3 | |
Total | 18 | 100 | 21 | 100 |
Of 18 episodes of PF (6 severe, 11 moderate, 1 mild) treated with Beth-P (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 Beth-P (Protein Hydrolysate) C deficiency were more effectively treated with Beth-P (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.
| Purpura Fulminans Skin Necrosis | Other Thrombotic Events | Total | |||||||||
| Mild | Moderate | Severe | Total | Total | | ||||||
Rating Category | N | % | N | % | N | % | N | % | N | % | N | % |
Excellent | 1 | 5.6 | 7 | 38.9 | 5 | 27.8 | 13 | 72.2 | 4 | 80.0 | 17 | 73.9 |
Good | 0 | 0.0 | 4 | 22.2 | 0 | 0.0 | 4 | 22.2 | 1 | 20.0 | 5 | 21.7 |
Fair | 0 | 0.0 | 0 | 0.0 | 1 | 5.6 | 1 | 5.6 | 0 | 0 | 1 | 4.3 |
Total | 1 | 5.6 | 11 | 61.1 | 6 | 33.3 | 18 | 100.0 | 5 | 100.0 | 23 | 100.0 |
N = Number of episodes |
In a secondary efficacy rating, 13 (72.2%) of the 18 episodes of PF treated with Beth-P (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.
Beth-P (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 Beth-P (Protein Hydrolysate) treatment, as shown in Table 6.
Lesion Type | Number of Episodes (Number of Subjects) | Mean | Median | Minimum | Maximum |
Non-necrotic | 16 (9 subjects) | 4.6 | 4.0 | 1 | 12 |
Necrotic | 7 (5 subjects) | 21.1 | 11.0 | 5 | 52 |
Changes in the extent of venous thrombus were also measured for the 5 thromboembolic episodes. Beth-P (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 Beth-P (Protein Hydrolysate) were free of complications of PF or thromboembolic events, as shown in Table 7.
Reason for Treatment | Number of Treatments | Presentation of Purpura Fulminans During Treatment Episodes | Thromboembolic Complications During Treatment Episode | Number of Treatments Free of Complications | |||
N | % | N | % | N | % | ||
Anticoagulation Therapy | 3 | 0 | 0.0 | 0 | 0.0 | 3 | 100.0 |
Surgical Procedure | 4 | 0 | 0.0 | 0 | 0.0 | 4 | 100.0 |
Total | 7 | 0 | 0.0 | 0 | 0.0 | 7 | 100.0 |
No episodes of PF occurred in four subjects ranging from 42 to 338 days of long-term prophylactic treatment with Beth-P (Protein Hydrolysate), as shown in Table 8. When not on prophylactic treatment and receiving Beth-P (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.
Summary Statistic | Long-Term Prophylactic Treatment | While On-Demand | Time to First Episode After Existing Long Term Prophylaxis | ||||
Number of Episodes per Subject | Number of Days Receiving Prophylactic Treatment | Monthly Rate of Episodes | Number of Episodes per Subject | Number of Days Not Receiving Study Drug | Monthly Rate of Episodes | ||
Mean | 0 | 229 | 0.0 | 3.3 | 165 | 1.91 | 23.3 |
Median | 0 | 268 | 0.0 | 3.0 | 159 | 0.49 | 24.5 |
Minimum | 0 | 42 | 0.0 | 1.0 | 19 | 0.25 | 12.0 |
Maximum | 0 | 338 | 0.0 | 6.0 | 323 | 6.40 | 32.0 |
A retrospective study to capture dosing information and treatment outcome data in subjects with severe congenital Beth-P (Protein Hydrolysate) C deficiency who were treated with Beth-P (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.
Beth-P (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 Beth-P (Protein Hydrolysate) C corresponds to the amidolytically measured activity of Beth-P (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).
Beth-P (Protein Hydrolysate) is available in single-dose vials that contain the following nominal product strengths:
NDC 0944-4177-05
Beth-P (Protein Hydrolysate) C
Concentrate (Human)
Beth-P (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
Beth-P (Protein Hydrolysate) C Concentrate
(Human)
Beth-P (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
Beth-P (Protein Hydrolysate) C
Concentrate (Human)
Beth-P (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
Beth-P (Protein Hydrolysate) C Concentrate (Human)
Beth-P (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:
Beth-P refers to a group of water-soluble vitamins. It has high biological activity. Beth-P (Vitamin B12) 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.
After oral administration Beth-P (Vitamin B12) 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.
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 Beth-P (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.
Beth-P is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Beth-P (Vitamin B12) 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 Beth-P (Vitamin B12) 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 Beth-P (Vitamin B12) 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.
CNS: rarely - a state of arousal.
Cardiovascular system: rarely - pain in the heart, tachycardia.
Allergic reactions: rarely - urticaria.
Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.
Cyanocobalamin can be used in pregnancy according to prescriptions.
When stenocardia should be used with caution in a single dose of Beth-P 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.
In an application of Beth-P (Vitamin B12) 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 Beth-P (Vitamin B12) 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.
Zinc Gluconate:
Beth-P (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Beth-P (Zinc Gluconate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.
None known.
Direct intramuscular or intravenous injection of Beth-P (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and Beth-P (Zinc Gluconate) doses because these elements are primarily eliminated in the urine.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Beth-P (Zinc Gluconate) from a bolus injection. Administration of Beth-P (Zinc Gluconate) in the absence of copper may cause a decrease in serum copper levels.
Periodic determinations of serum copper as well as Beth-P (Zinc Gluconate) are suggested as a guideline for subsequent Beth-P (Zinc Gluconate) administration.
Long-term animal studies to evaluate the carcinogenic potential of Beth-P 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Beth-P (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
Pregnancy Category C. Animal reproduction studies have not been conducted with Beth-P chloride. It is also not known whether Beth-P (Zinc Gluconate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Beth-P (Zinc Gluconate) chloride should be given to a pregnant woman only if clearly needed.
An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
None known.
None known.
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Beth-P (Zinc Gluconate) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Beth-P (Zinc Gluconate) concentration of 207 mcg/dl. Symptoms abated within three hours.
Hyperamylasemia may be a sign of impending Beth-P (Zinc Gluconate) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).
Death resulted from an overdosage in which 1683 mg Beth-P (Zinc Gluconate) was delivered intravenously over the course of 60 hours to a 72 year old patient.
Symptoms of Beth-P (Zinc Gluconate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Beth-P (Zinc Gluconate) level of 4184 mcg/dl.
Calcium supplements may confer a protective effect against Beth-P (Zinc Gluconate) toxicity.
Beth-P (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Beth-P (Zinc Gluconate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Beth-P (Zinc Gluconate).
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
Beth-P (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
Revised: October, 2004
© Hospira 2004 EN-0488 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
10 mL Vial
Beth-P (Zinc Gluconate)
1 mg/mL
Beth-P (Zinc Gluconate) Chloride Inj., USP
Rx only
FOR I.V. USE ONLY AFTER DILUTION.
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
Depending on the reaction of the Beth-P after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Beth-P not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Beth-P addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
There are no reviews yet. Be the first to write one! |
The information was verified by Dr. Rachana Salvi, MD Pharmacology