Compost-A-Pak®'s product development and manufacturing processes are driven by our sustainability goals.
All products are made from a natural starch-based polymer derived from corn. They are completely plastic free!
We choose corn, as it's an annually renewable resource, unlike trees which can take years to mature. Our corn is sourced from international GMO-free regions with high levels of natural rainfall to minimise irrigation, and we deliberately select third grade corn. This corn is essentially spoilt corn, and so is unsuitable for human or animal consumption.
Blown film bags are then manufactured in a range of sizes and styles on purpose built equipment, which has been reengineered to minimise electricity consumption. Compost-A-Pak liners are then printed with soy-based, non-toxic printing inks.
Designed initially to collect organic kitchen waste, Compost-A-Pak® liners are proven to significantly improve waste diversion in large council programs, simply by making it so much more convenient to collect and transport organic waste. With over 50% of Australian household waste organic, reducing the amount sent to landfill can have a significantly positive environmental benefit, and contribute towards reducing the risk of landfill, including the omission of gasses linked to global warming.
Compost-A-Pak®'s products are Australian Certified compostable, for both home composting and industrial composting facilities. The liners breakdown with the organic waste through microbial activity, in the same way as their parent plants, creating a rich soil enhancing compost, perfect for the family vegetable patch, or, in commercial quantities, for organic farming.
Importantly, the nutrients taken in the harvesting of corn for manufacturing our bags, can then be returned to the Earth as compost for future crops.
Compost-A-Pak® is an Australian family owned business. Working alongside our fabulous, passionate team, we are genuinely motivated by ethics, the environment, and a simple commitment to make the world a better place.
Compost-A-Pak® liners are manufactured in a range of convenient sizes, and are consistently high quality, manufactured to a strict minimum um (thickness) standard. Scientifically tested, with millions of bags in use, this unique minimum standard ensures you can be confident that you have the quality required to collect and transport organic waste with minimum breakages and tears.
We are incredibly proud that our high quality liners are made of a renewable material, are Australian Certified compostable, and are assisting to improve the Australian environment, both for our children and future generations.
In quiet moments of reflection, away from phones and emails, there are certain things that you realise are really important, things that we believe also resonate with our customers.
Committed to making the world a better place, we have launched a program specifically to support Australia's unique flora, and we are hoping to inspire you to get involved.
As part of this program, when you order with us, we are asking you to also accept a satchel of rare Australian flora seeds. We will simply add it to your order! All we ask is for you to commit to plant the seeds and care for the resulting Australian wildflower, perhaps even nourishing them with the fabulous compost from your organic waste.
Our aim is to not just spread seeds, but share our passion for Australian Natives and an increased awareness of their importance in our unique ecosystems.
Golden Everlasting Daisy, the gorgeous Australian wildflower depicted in the background.
Classification: Listed as Declared Rare Flora under the Western Australian Wildlife Conservation Act 1950.
Details: An attractive perennial plant with large golden blooms which last several months. Excellent for fresh cut flowers or for drying, so you can even gift natives to your family and friends, and spread the word about preserving Australia's precious natives.
Find a spot with full sun or part shade in rich well-drained soil. Mixing compost with your soil will assist with the soil quality and water retention. Sow in warm areas at any time, or in colder climates wait until the danger of frost is over.
Sprinkle seeds thinly and lightly press into surface of the soil. Water, and then keep evenly moist with regular water until they are established. Now the exciting stage – Seedlings will emerge in 7-10 days, and plant will grow up to 1 meter high.
If using seed trays initially.
Alternatively, you can place seed into seed trays filled with a moist quality seed raising mix. Cover the trays with clear plastic to preserve moisture and warmth – remove when germination commences. Place in a warm shaded position to germinate fully. Transplant when plants about 7cm high, spacing plants 30cm apart.
Pick for drying just before buds open, strip off all leaves, hang upside down in loose bunches in a dark place until completely dry.
OUR STORY HAS GROWN THROUGH COLLABORATIONS AND FRIENDSHIPS. WE WOULD LOVE TO HEAR YOUR THOUGHTS ABOUT OUR PRODUCTS AND IDEAS FOR A MORE SUSTAINABLE FUTURE.
https://compostapak.com.au/wp-content/uploads/2019/01/20181216_111335-1.jpg 2412 2412 admin https://compostapak.com.au/wp-content/uploads/2016/12/compost-a-pak-logo-top-logo.png admin2019-01-24 14:11:262019-01-24 14:36:41Everyday Sustainable Practices!


text:
Adakveo 10 mg/ml concentrate for solution for infusion
Novartis Pharmaceuticals UK Ltd contact details
crizanlizumab
Last updated on emc: 06 Oct 2021
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.
Adakveo® 10 mg/ml concentrate for solution for infusion
Each ml of concentrate for solution for infusion contains 10 mg crizanlizumab.
One vial of 10 ml contains 100 mg crizanlizumab.
Crizanlizumab is a monoclonal antibody produced in Chinese Hamster Ovary (CHO) cells by recombinant DNA technology.
Concentrate for solution for infusion (sterile concentrate)
Colourless to slightly brownish-yellow liquid at pH 6 and with an osmolality of 300 mOsm/kg.
Adakveo is indicated for the prevention of recurrent vaso-occlusive crises (VOCs) in sickle cell disease patients aged 16 years and older. It can be given as an add-on therapy to hydroxyurea/hydroxycarbamide (HU/HC) or as monotherapy in patients for whom HU/HC is inappropriate or inadequate.
Treatment should be initiated by physicians experienced in the management of sickle cell disease.
The recommended dose of crizanlizumab is 5 mg/kg administered over a period of 30 minutes by intravenous infusion at week 0, week 2, and every 4 weeks thereafter.
Crizanlizumab can be given alone or with HU/HC.
If a dose is missed, the treatment should be administered as soon as possible.
- If crizanlizumab is administered within 2 weeks after the missed dose, dosing should be continued according to the patient's original schedule.
- If crizanlizumab is administered more than 2 weeks after the missed dose, dosing should be continued every 4 weeks thereafter.
Crizanlizumab has not been studied in elderly patients. No dose adjustment is required as the pharmacokinetics of crizanlizumab in adults are not affected by age.
Based on the population pharmacokinetic (PK) results, no dose adjustment is required in patients with mild or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment are too limited to draw conclusions on this population.
Hepatic impairment
The safety and efficacy of crizanlizumab in patients with hepatic impairment have not been established. Crizanlizumab is a monoclonal antibody and is cleared via catabolism (i.e. breakdown into peptides and amino acids), and a change in dose is not expected to be required for patients with hepatic impairment (see section 5.2).
The safety and efficacy of crizanlizumab in paediatric patients from 6 months to 16 years have not been established. No data are available.
There is no relevant use of crizanlizumab in infants aged less than 6 months for the indication of prevention of recurrent vaso-occlusive crises.
Adakveo should be diluted with sodium chloride 9 mg/ml (0.9%) solution for injection or dextrose 5% before administration.
The diluted solution must be administered through a sterile, non-pyrogenic 0.2 micron in-line filter by intravenous infusion over a period of 30 minutes. It must not be administered by intravenous push or bolus.
For instructions on dilution of the medicinal product before administration, see section 6.6.
Hypersensitivity to Chinese Hamster Ovary (CHO) cell products.
Infusion-related reactions
In clinical studies, infusion-related reactions (defined as occurring within 24 hours) were observed in 2 patients (1.8%) treated with crizanlizumab 5 mg/kg. Patients should be monitored for signs and symptoms of infusion-related reactions, which may include fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath or wheezing. In the event of a severe reaction, crizanlizumab should be discontinued and appropriate therapy should be instituted.
Laboratory test interference: automated platelet counts
Interference with automated platelet counts (platelet clumping) has been observed in patients treated with crizanlizumab in clinical studies, in particular when tubes containing EDTA (ethylenediaminetetraacetic acid) were used. This may lead to unevaluable or falsely decreased platelet counts. There is no evidence that crizanlizumab causes a reduction in circulating platelets or has a pro-aggregant effect in vivo.
To mitigate the potential for laboratory test interference, it is recommended to run the test as soon as possible (within 4 hours of blood collection) or use citrate tubes. When needed, platelet counts can be estimated via a peripheral blood smear.
Excipients with known effect
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially "sodium-free".
Interactions between crizanlizumab and other medicinal products have not been investigated in dedicated studies.
Monoclonal antibodies are not metabolised by cytochrome P450 (CYP450) enzymes. Therefore, medicinal products that are substrates, inhibitors or inducers of CYP450 are not expected to affect the pharmacokinetics of crizanlizumab. In clinical studies, HU/HC had no effect on crizanlizumab pharmacokinetics in patients.
No effect on exposure of co-administered medicinal products is expected based on the metabolic pathways of monoclonal antibodies.
There is a limited amount of data from the use of Adakveo in pregnant women. Based on data from animal studies, crizanlizumab has the potential to cause foetal losses when administered to a pregnant woman (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Adakveo during pregnancy and in woman of childbearing potential not using contraception.
To help determine the effects in pregnant women, healthcare professionals are encouraged to report all pregnancy cases and complications during pregnancy (from 105 days prior to the last menstrual period onward) to the local representative of the marketing authorisation holder (see package leaflet), in order to allow monitoring of these patients through the PRegnancy outcomes Intensive Monitoring programme (PRIM). In addition, all adverse pregnancy events should be reported via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store..
It is unknown whether crizanlizumab is excreted in human milk after administration of Adakveo. There are no data on the effects of crizanlizumab on the breast-fed newborn/infant or on milk production.
Because many medicinal products, including antibodies, can be excreted in human milk, a risk to the newborn/infant cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue Adakveo therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
There are no data on the effect of Adakveo on human fertility. Available non-clinical data do not suggest an effect on fertility under crizanlizumab treatment (see section 5.3).
Adakveo may have a minor influence on the ability to drive and use machines. Dizziness, fatigue and somnolence may occur following administration of crizanlizumab.
The most frequently reported adverse drug reactions (≥10% of patients) in the Adakveo 5 mg/kg group were arthralgia, nausea, back pain, pyrexia and abdominal pain. Severe events were observed for pyrexia and arthralgia (each 0.9%).
Table 1 lists adverse reactions based on pooled data from two studies: the pivotal study, SUSTAIN, and a single-arm, open-label pharmacokinetics/pharmacodynamics and safety study. Use of crizanlizumab in combination with HU/HC did not result in any meaningful differences in the safety profile.
Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
Table 1 Adverse reactions in clinical studies
Adverse reaction
Oropharyngeal pain
Nausea, abdominal pain*
Diarrhoea, vomiting
Pruritus*
Arthralgia, back pain
Myalgia, musculoskeletal chest pain
Pyrexia
Infusion site reaction*
Injury, poisoning and procedural complications
Infusion-related reaction
*The following groupings contain the following MedDRA preferred terms:
- Abdominal pain: abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, and abdominal tenderness
- Pruritus: pruritus and vulvovaginal pruritus
- Infusion site reaction: infusion site extravasation, infusion site pain, and infusion site swelling
In clinical studies, treatment-induced anti-crizanlizumab antibodies were transiently detected in 1 patient (0.9%) among the 111 patients who received Adakveo 5 mg/kg.
There was no evidence of altered pharmacokinetics or of an altered safety profile with anti-crizanlizumab antibody development.
Frequency, type and severity of adverse reactions in patients aged 16 and 17 years are expected to be the same as in adults. The safety of crizanlizumab was evaluated in 3 patients aged <18 years.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store..
No cases of overdose have been reported in clinical studies.
General supportive measures and symptomatic treatment should be initiated in cases of suspected overdose.
Pharmacotherapeutic group: Other haematological agents, ATC code: B06AX01
Crizanlizumab is a selective IgG2 kappa humanised monoclonal antibody (mAb) that binds to P-selectin with high affinity and blocks the interaction with its ligands, including P-selectin glycoprotein ligand 1. Crizanlizumab can also dissociate preformed P-selectin/PSGL-1 complex. P-selectin is an adhesion molecule expressed on activated endothelial cells and platelets. It plays an essential role in the initial recruitment of leukocytes and the aggregation of platelets to the site of vascular injury during inflammation. In the chronic pro-inflammatory state associated with sickle cell disease, P-selectin is over-expressed and circulating blood cells and the endothelium are activated and become hyperadhesive. P-selectin-mediated multi-cellular adhesion is a key factor in the pathogenesis of vaso-occlusion and vaso-occlusive crises (VOC). Elevated levels of P-selectin are found in patients with sickle cell disease.
Binding P-selectin on the surface of the activated endothelium and platelets has been shown to effectively block interactions between endothelial cells, platelets, red blood cells and leukocytes, thereby preventing vaso-occlusion.
Throughout clinical studies, treatment with crizanlizumab 5 mg/kg resulted in dose-dependent, immediate and sustained P-selectin inhibition (as measured ex vivo) in patients with sickle cell disease.
The efficacy of crizanlizumab, with or without HU/HC, was evaluated in the pivotal study SUSTAIN, a 52-week, randomised, placebo-controlled, double-blind, multicentre clinical study in sickle cell disease patients with a history of vaso-occlusive crises (VOCs).
In this study, VOCs were defined as those leading to a healthcare visit, which captured all acute episodes of pain with no other cause than a vaso-occlusive event that required a healthcare visit and treatment with oral or parenteral opioids or parenteral non-steroidal anti-inflammatory drugs (NSAIDs). Acute chest syndrome, hepatic sequestration, splenic sequestration and priapism (requiring a healthcare visit), by definition, were also considered VOCs.
A total of 198 sickle cell disease patients aged 16 to 63 years (inclusive; mean age 30.1±10.3 years), with any sickle cell disease genotype (including HbSS [71.2%], HbSC [16.2%], HbSbeta0-thalassaemia [6.1%], HbSbeta+-thalassaemia [5.1%], and others [1.5%]) and a history of between 2 and 10 VOCs in the previous 12 months (62.6% and 37.4% of the patients had 2-4 or 5-10 VOCs, respectively), were randomised 1:1:1 to Adakveo 5 mg/kg, Adakveo 2.5 mg/kg or placebo. The majority of patients were Black or African American (91.9%). Patients received Adakveo with (62.1%) or without (37.9%) HU/HC. Randomisation was stratified by patients already receiving HU/HC (Y/N) and by number of VOCs in the previous 12 months (2 to 4, 5 to 10). Patients were allowed to take medicinal products to relieve pain (i.e. paracetamol, NSAIDs and opioids) and to receive occasional transfusions on an "as needed" basis. Patients participating in a chronic transfusion programme (pre-planned series of transfusions for prophylactic purposes) were excluded from the study.
Treatment with Adakveo 5 mg/kg resulted in a 45.3% lower median annual rate of VOCs compared to placebo (Hodges-Lehmann, median absolute difference of -1.01 compared with placebo, 95% CI [-2.00, 0.00]), which was statistically significant (p=0.010). The median annual rates of uncomplicated VOCs (any VOCs as defined above, excluding acute chest syndrome, hepatic sequestration, splenic sequestration or priapism) and days hospitalised were 62.9% and 41.8% lower in the Adakveo 5 mg/kg than in the placebo group, respectively. The VOCs occurring during the study were assessed by an independent review committee.
Main efficacy outcomes of the pivotal SUSTAIN study are summarised in Tables 2 and 3.
Table 2 Results from SUSTAIN clinical study in sickle cell disease
Adakveo 5 mg/kg
(N=67)
(standard median)
Change vs placebo
Hodges-Lehmann median difference
(95% CI)
(Wilcoxon rank sum)
Primary endpoint
Annual rate of VOCs
(-2.00, 0.00)
Secondary endpoints
Annual rate of days hospitalised
Annual rate of uncomplicated VOCs
The primary (annual rate of VOC leading to healthcare visit) and key secondary (annual rate of days hospitalised) endpoints were the only ones formally tested for statistical significance according to protocol.
The clinical effect demonstrated in the primary efficacy analysis was supported by multiple supplementary analyses including a negative binomial regression on investigator assessments with a conservative method to handle missing data due to early discontinuation of treatment based on outcomes in the placebo group (RR=0.74, 95% CI=0.52, 1.06).
In the Adakveo 5 mg/kg group, clinically significant reductions in the annual rate of VOCs were observed across important subgroups (HU/HC use, 2-4 or 5-10 VOCs in the previous 12 months, and HbSS or non-HbSS genotypes; see Table 3).
Table 3 Annual rate of VOCs in patients - subgroup analyses
HU/HC use
n= 40
Number of VOCs in previous 12 months
2-4 VOCs
5-10 VOCs
(-5.00, -0.83)
Sickle cell disease genotypes, including HbSC
HbSS
Non-HbSS
A greater than two-fold increase in the proportion of patients with no VOC and who completed the study was observed in the Adakveo 5 mg/kg group compared to placebo (22% vs 8%; odds ratio [95% CI]: 3.57 [1.20, 10.63]). A similar difference was also observed across important subgroups (HU/HC use, genotype).
Treatment with Adakveo 5 mg/kg was also associated with a three-fold longer Kaplan-Meier estimated median time to first VOC compared with placebo (4.07 vs 1.38 months; HR=0.495, 95% CI: 0.331, 0.741) (Figure 1) and a two-fold longer median time from randomisation to second VOC compared to placebo (10.32 vs 5.09 months; HR=0.534, 95% CI: 0.329, 0.866).
Figure 1 Kaplan-Meier curve of time to first VOC
The efficacy of crizanlizumab in patients aged 16 and 17 years is expected to be the same as in adults. Three patients (2.7%) aged less than 18 years were treated with crizanlizumab 5 mg/kg in clinical studies.
The European Medicines Agency has deferred the obligation to submit the results of studies with Adakveo in one or more subsets of the paediatric population in the treatment of sickle cell disease (see section 4.2 for information on paediatric use).
Conditional approval
This medicinal product has been authorised under a so-called "conditional approval" scheme. This means that further evidence on this medicinal product is awaited.
The European Medicines Agency will review new information on this medicinal product at least every year and this SmPC will be updated as necessary.
The median time to reach maximum serum concentration of crizanlizumab (Tmax) was 1.92 hours at steady state following intravenous administration of 5 mg/kg over a period of 30 minutes in sickle cell disease patients.
Crizanlizumab distribution is typical of endogenous human antibodies within the vascular and extracellular spaces. The volume of distribution (Vz) was 4.26 litres after a single 5 mg/kg intravenous infusion of crizanlizumab in healthy volunteers.
Antibodies are primarily eliminated via proteolysis by lysosomal enzymes in the liver to small peptides and amino acids.
In healthy volunteers, the mean terminal elimination half-life (T½) was 10.6 days and the mean clearance was 11.7 ml/h at crizanlizumab dose level 5 mg/kg. In patients with sickle cell disease, the mean elimination T½ during the dosing interval was 7.5 days.
The exposure to crizanlizumab (mean Cmax, AUClast, or AUCinf) increased in non-linear manner over the dose range of 0.2 to 8 mg/kg in healthy volunteers.
In a population PK analysis in patients with eGFR ranging from 35 to 202 ml/min/1.73 m2, no clinically important differences in the pharmacokinetics of crizanlizumab were found between patients with mild or moderate renal impairment and patients with normal renal function. Data from patients with severe renal impairment are too limited to draw conclusions on this population (see section 4.2).
The safety and efficacy of crizanlizumab in patients with hepatic impairment have not been established. Crizanlizumab is a monoclonal antibody and is cleared via catabolism (i.e. breakdown into peptides and amino acids), and a change in dose is not expected to be required for patients with hepatic impairment.
Pharmacokinetics in paediatric patients below the age of 16 years have not been investigated.
Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, tissue cross-reactivity and repeated dose toxicity.
In the 26-week repeated dose toxicity study, administration of crizanlizumab in cynomolgus monkeys at dose levels up to 50 mg/kg/dose once every 4 weeks (at least 13.5 times the human clinical exposure based on AUC in patients with sickle cell disease at 5 mg/kg once every four weeks) was generally well tolerated. There were no primary crizanlizumab-related findings on any endpoint evaluated. At 50 mg/kg, minimal to moderate inflammation of the vessels in multiple tissues considered to be an antigen-antibody complex reaction (primate antihuman antibody) was observed in 2 of 10 animals. There was one death attributed to aspiration of gastric contents following a peri-infusional reaction mediated by anti-drug-antibody-dependent hypersensitivity.
Pharmacological effects of crizanlizumab on haemodynamic and electrocardiographic parameters in the cynomolgus monkey were evaluated in the 26-week repeated dose toxicology study. Respiratory rate and neurological parameters were also assessed. There were no crizanlizumab-related effects on arterial blood pressure or on heart rate, PR, RR, QRS, QT, and heart rate corrected QT (QTc) intervals on the electrocardiograms (ECG). No rhythm abnormalities or qualitative changes were observed during the qualitative ECG assessment. There were no crizanlizumab-related effects on respiration rate or any neurological parameter evaluated.
Formal carcinogenicity, genotoxicity and juvenile toxicity studies have not been conducted with crizanlizumab.
In a 26-week repeated dose toxicity study, cynomolgus monkeys were administered crizanlizumab once every 4 weeks at doses up to 50 mg/kg (at least 13.5 times the human clinical exposure based on AUC in patients with sickle cell disease at 5 mg/kg once every four weeks). There were no adverse effects of crizanlizumab on male and female reproductive organs.
In an enhanced pre- and postnatal development study in cynomolgus monkeys, pregnant animals received intravenous crizanlizumab once every two weeks during the period of organogenesis, at doses of 10 and 50 mg/kg (approximately 2.8 and 16 times the human clinical exposure based on AUC in patients with sickle cell disease at 5 mg/kg/dose once every four weeks, respectively). No maternal toxicity was observed. There was an increase in foetal loss (abortions or stillbirths) at both doses and this was higher in the third trimester. The cause of the foetal losses in monkeys is unknown but may be due to the development of anti-drug antibodies against crizanlizumab. There were no effects on infant growth and development during the 6 months postpartum that were attributable to crizanlizumab.
Measurable crizanlizumab serum concentrations were observed in the infant monkeys at postnatal day 28, confirming that crizanlizumab, like other IgG antibodies, crosses the placental barrier.
Sodium citrate (E331)
Citric acid (E330)
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Unopened vial
Diluted solution
Chemical and physical in-use stability, from the start of preparation of the diluted solution for infusion until end of infusion, has been demonstrated for up to 8 hours at room temperature (up to 25°C) and at 2°C to 8°C for up to 24 hours overall.
From a microbiological point of view, the diluted solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, including 4.5 hours at room temperature (up to 25°C) from the start of preparation to completion of the infusion, unless dilution has taken place in controlled and validated aseptic conditions.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
10 ml concentrate for solution for infusion in a type I glass vial with a coated chlorobutyl rubber stopper sealed with an aluminium cap with a plastic flip-off disk containing 100 mg crizanlizumab.
Pack of 1 vial.
Adakveo vials are for single use only.
Preparing the infusion
The diluted solution for infusion should be prepared by a healthcare professional using aseptic techniques.
The total dose and required volume of Adakveo depend on the patient's body weight; 5 mg of crizanlizumab is administered per kg body weight.
The volume to be used for the preparation of the infusion is calculated according to the following equation:
Volume (ml) =
Patient's body weight (kg) x prescribed dose
[5 mg/kg]
Concentration of Adakveo
[10 mg/ml]
1. Obtain the number of vials required to deliver the prescribed dose and bring them to room temperature (for a maximum of 4 hours). One vial is needed for every 10 ml of Adakveo (see below table).
Body weight (kg)
Dose (mg)
Vials (n)
2. Visually inspect the vials.
- The solution in the vials should be clear to opalescent. Do not use if particles are present in the solution.
- The solution should be colourless or may have a slight brownish-yellow tint.
3. Withdraw a volume equal to the required volume of Adakveo from a 100 ml infusion bag containing either sodium chloride 9 mg/ml (0.9%) solution for injection or dextrose 5% and discard.
- No incompatibilities between the diluted Adakveo solution and infusion bags composed of polyvinylchloride (PVC), polyethylene (PE) and polypropylene (PP) have been observed.
4. Withdraw the necessary volume of Adakveo from the vials and inject slowly into the previously prepared infusion bag.
- The solution must not be mixed or co-administered with other medicinal products through the same intravenous line.
- Keep the volume of Adakveo added to the infusion bag in the range of 10 ml to 96 ml to obtain a final concentration in the infusion bag within 1 mg/ml to 9.6 mg/ml.
5. Mix the diluted solution by gently inverting the infusion bag. DO NOT SHAKE.
Adakveo diluted solution must be administered through a sterile, non-pyrogenic 0.2 micron in-line filter by intravenous infusion over a period of 30 minutes. No incompatibilities have been observed between Adakveo and infusion sets composed of PVC, PE-lined PVC, polyurethane, and in-line filter membranes composed of polyethersulfone (PES), polyamide (PA) or polysulphone (PSU).
After administration of Adakveo, flush the line with at least 25 ml sodium chloride 9 mg/ml (0.9%) solution for injection or dextrose 5%.
Novartis Pharmaceuticals UK Limited
2nd Floor, The WestWorks Building, White City Place
195 Wood Lane
W12 7FQ
PLGB 00101/1191
Novartis Pharmaceuticals UK Ltd
2nd Floor, The WestWorks Building, White City Place, 195 Wood Lane, London, W12 7FQ

redpajama_set_name: RedPajamaCommonCrawl


text:
Keyword: Early Middle Ages
Perchement et Réalités Fortifiées en Méditerranée et en Europe, Vème-Xème Siècles
ed. Philippe Pergola et al.
Limina/Limites: Archaeologies, histories, islands and borders in the Mediterranean (365-1556) 11
The result of an international congress (Roquebrune-sur-Argens, October 2019) about the fortified hilltop settlements of Late Antiquity and the Early Middle Ages, papers present both brand new data and syntheses on wide contexts throughout the European continent, the Mediterranean basin and beyond. READ MORE
Archaeologies & Antiquaries: Essays by Dai Morgan Evans
David Morgan Evans et al.
This book collects and republishes 14 key academic works by Dai Morgan Evans FSA (1944–2017). Spanning early medieval studies, the management and conservation of ancient monuments, histories of antiquarianism, and the Welsh church of Llangar, the chapters have been freshly edited and published together for the first time with new illustrations. READ MORE
Paisajes, espacios y materialidades: Arqueología rural altomedieval en la península ibérica
ed. Sara Prata et al.
Rural landscapes are increasingly important when analysing the processes of change following the collapse of the Roman imperial structure. This volume presents contributions from key researchers in early medieval peasant archaeology in the north-western quadrant of the Peninsula, offering a multi-scale image of the main lines of ongoing research. READ MORE
Paperback: £48.00 | Free Download | eBook Institution: £9.99
Interdisciplinary Research into Iron Metallurgy along the Drava River in Croatia
ed. Tajana Sekelj Ivančan et al.
Presenting the results of the TransFER project, this study uses a wide-ranging methodology to examine the evidence for, and nature of, iron production in the lowland area of the central Drava River basin in Croatia during late Antiquity and the early Middle Ages. The results testify to the importance and longevity of iron production in the area. READ MORE
Dinamiche insediative nelle campagne dell'Italia tra Tarda Antichità e Alto Medioevo
ed. Angelo Castrorao Barba
Limina/Limites: Archaeologies, histories, islands and borders in the Mediterranean (365-1556) 6
A series of selected contributions about settlement patterns in the Italian countryside between Late Antiquity and the Early Middle Ages, providing a critical overview of the most recent research on the subject. READ MORE


text:
package org.elasticsearch.rest.action.admin.indices;

import org.elasticsearch.action.admin.indices.template.put.PutComposableIndexTemplateAction;
import org.elasticsearch.client.node.NodeClient;
import org.elasticsearch.cluster.metadata.ComposableIndexTemplate;
import org.elasticsearch.rest.BaseRestHandler;
import org.elasticsearch.rest.RestRequest;
import org.elasticsearch.rest.action.RestToXContentListener;

import java.io.IOException;
import java.util.List;

import static org.elasticsearch.rest.RestRequest.Method.POST;
import static org.elasticsearch.rest.RestRequest.Method.PUT;

public class RestPutComposableIndexTemplateAction extends BaseRestHandler {

    @Override
    public List<Route> routes() {
        return List.of(
            new Route(POST, "/_index_template/{name}"),
            new Route(PUT, "/_index_template/{name}"));
    }

    @Override
    public String getName() {
        return "put_composable_index_template_action";
    }

    @Override
    public RestChannelConsumer prepareRequest(final RestRequest request, final NodeClient client) throws IOException {

        PutComposableIndexTemplateAction.Request putRequest = new PutComposableIndexTemplateAction.Request(request.param("name"));
        putRequest.masterNodeTimeout(request.paramAsTime("master_timeout", putRequest.masterNodeTimeout()));
        putRequest.create(request.paramAsBoolean("create", false));
        putRequest.cause(request.param("cause", "api"));
        putRequest.indexTemplate(ComposableIndexTemplate.parse(request.contentParser()));

        return channel -> client.execute(PutComposableIndexTemplateAction.INSTANCE, putRequest, new RestToXContentListener<>(channel));
    }
}

redpajama_set_name: RedPajamaGithub