Consumer medicine information

PROLASTIN C

Alpha-1-proteinase inhibitor

BRAND INFORMATION

Brand name

Prolastin-C

Active ingredient

Alpha-1-proteinase inhibitor

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using PROLASTIN C.

What is in this leaflet

Please read this leaflet carefully before you start using PROLASTIN-C (prō-‘lǎs-tĭn).

This leaflet answers some common questions about PROLASTIN-C, a prescription medicine. It does not contain all the available information. It does not take the place of talking to your doctor.

All medicines have risks and benefits. Your doctor has weighed the risks of you using PROLASTIN-C against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor.

Keep this leaflet with you. You may need to read it again.

What Prolastin C is used for

PROLASTIN-C is used to treat Alpha1-PI Deficiency. This is a genetic disorder. It is characterised by very low amounts of your own alpha-1-proteinase inhibitor protein (Alpha1-PI) in your lungs. Some patients develop a serious lung disease called emphysema.

PROLASTIN-C contains human Alpha1-PI manufactured from blood products. You take PROLASTIN-C to boost Alpha1-PI in your bloodstream and lungs.

One of the reasons your lungs have been damaged is because you lack enough of Alpha1-PI. Other causes include smoking and infections. Alpha1-PI inhibits enzymes that break down lung tissue. Be aware that there are no medical studies in people to prove that taking PROLASTIN-C over a long period of time will stop or slow down the symptoms of emphysema.

Before you use Prolastin C

When you must not use it

Do not use PROLASTIN-C if you know you lack immunoglobulin A (IgA) in your bloodstream and your body has made its own antibodies against IgA. You could have a bad allergic reaction to PROLASTIN-C because it contains trace amounts of IgA.

Smoking is not recommended during your treatment with PROLASTIN-C

If you are not sure whether you should use PROLASTIN-C, talk to your doctor

Before you start to use it

Tell your doctor if:

  • You are pregnant or intend to become pregnant. It is not known whether PROLASTIN-C is harmful to an unborn baby when given to a pregnant woman.
  • You are breastfeeding. Many medicines are excreted into the human breast milk.
  • You do not tolerate medicines made from blood.
  • You are concerned that your child may be treated with PROLASTIN-C. The safety and effectiveness of PROLASTIN-C in children have not been established.
  • You are a smoker as the effectiveness of PROLASTIN-C in smokers has not been established.

If you have not told your doctor about any of the above, tell your doctor before you are treated with PROLASTIN-C.

Your body may not tolerate PROLASTIN-C if you have the very rare condition of “IgA deficiency” and your body has already made its own antibodies against immunoglobulin A (IgA). If your doctor suspects that you are experiencing an allergic or anaphylactic reaction during administration of PROLASTIN-C, your doctor must immediately discontinue the injection.

Special safety warning

When medicines are made from human blood plasma, certain measures are put in place to prevent infections from viruses or the Creutzfeldt-Jakob disease (CJD) agent from being passed on to patients. These include

  • Carefully selecting blood and plasma donors to make sure those at risk of carrying infections are excluded.
  • Testing of each donation and pools of plasma for signs of virus or virus infections.
  • Including steps in the processing of the blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This applies to any unknown or emerging viruses or other types of infections.

Discuss the risks and benefits of this medicine with your doctor before using it.

Talk to your doctor if you become sick with a virus infection. Your doctor or you may want to report the infection to Grifols Australia Pty Ltd 1800 339 479.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop. You should also tell any health professional who is prescribing a new medicine for you that you are using PROLASTIN-C.

Your doctor has more information on medicines to be careful with or avoid while using PROLASTIN-C. Interactions with other medicines are not known.

How to use Prolastin C

How much to Use

Your doctor will decide the amount of PROLASTIN-C that is right for you. A standard dose is 60 milligrams of PROLASTIN-C for every 1 kilogram of body weight. A doctor, nurse or other caregiver trained to give injections will give you the infusion. Your doctor must inject PROLASTIN-C into a blood vessel (intravenously). Your doctor should observe you or your infant for at least 20 minutes afterward. If you are receiving PROLASTIN-C infusions at home, rather than in a hospital or clinic, be sure to closely follow all instructions from your doctor.

When to use it

Your doctor will determine when your treatments should be given. The standard schedule is weekly. The infusion takes approximately 15 minutes.

How long to use it

You will use PROLASTIN-C weekly until your doctor tells you otherwise.

If you forget to use it

If you miss a scheduled infusion of PROLASTIN-C, talk to your doctor about rescheduling.

While you are using Prolastin C

Things you must do

If you are about to be started on any new medicine tell your doctor that you are using PROLASTIN-C.

Things you must not do

Do not give PROLASTIN-C to anyone else, even if they have the same condition as you.

Things to be careful of

No effects on ability to drive and use machines have been observed with PROLASTIN-C.

In case of overdose

If you use too much (overdose)

There have been no reported cases of overdose for PROLASTIN-C. No data are available concerning overdose in humans.

Immediately telephone your doctor or the National Poisons Centre (telephone 0800 POISON or 0800 764 766), or go to accident and emergency at your nearest hospital, if you think that you or anyone else may have taken too much PROLASTIN-C.

Do this even if there are no signs of discomfort or poisoning.

Side effects

Tell your doctor as soon as possible if you do not feel well after being treated with PROLASTIN-C.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the known adverse effects.

Ask your doctor to answer any questions you may have.

Tell your doctor if any of the following side effects happen during or soon after the infusion.

  • Headache
  • Dizziness
  • Fatigue
  • Shortness of breath (dyspnea)
  • Hives (urticaria) or rash

Occasionally, you may experience:

  • Chills
  • Chest discomfort or pain
  • Out of sorts feeling (malaise)
  • Itching (pruritus)
  • Allergic or anaphylactic type reactions including shock
  • Influenza-like illness

Rarely, you may experience:

  • Racing heartbeat (tachycardia)

There is a possibility that your body could react to PROLASTIN-C. Allergic reactions to PROLASTIN-C have occurred. If you go into shock, your doctor will treat you by following standard guidelines for shock therapy.

Other adverse effects not listed above may also occur in some patients. Tell your doctor if you notice any other side effects or if any of the above side effects get serious.

Do not be alarmed by this list of possible adverse effects. You may not experience any of them.

After using Prolastin C

Storage

Your doctor must store PROLASTIN-C at or below 25°C, and never in a freezer. Your doctor must use PROLASTIN-C on or before the expiry date stamped on the label.

Your doctor must never use PROLASTIN-C that was ever frozen, is cloudy or has particles in it.

All medicines, including PROLASTIN-C, must be kept out of reach of children.

Disposal

Your doctor will dispose of any unused or expired medicine or medical waste in accordance with local requirements.

Medicines should not be disposed of into wastewater or household waste. Ask your doctor or pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Product description

What it looks like

PROLASTIN-C is a white to beige-coloured powder in a glass vial. It comes in a kit with a second vial of 20 millilitres of Sterile Water for Injection, USP, which is used to dissolve PROLASTIN-C. The kit also contains a sterile double-sided needle to transfer the water into the PROLASTIN-C vial, and a filter needle.

Ingredients

Active ingredient:

  • Alpha-1-proteinase inhibitor (human)

Inactive ingredients:

  • Sodium chloride, USP
  • Sodium phosphate – monobasic, USP
  • Sterile Water for Injection, USP

PROLASTIN-C is sterile and does not contain an antimicrobial preservative.

Sponsor details

Grifols Australia Pty Ltd
Unit 5/80 Fairbank Road, Clayton South, VIC 3169
Australia

Manufactured by:
Grifols Therapeutics Inc.
Clayton, North Carolina, 27520 USA

Australian Registration Number

Prolastin-C
1,000 milligrams, Powder for Reconstitution for Injection

AUST R 234553

Date of preparation

This leaflet was prepared on 16 November 2016

Published by MIMS March 2017

BRAND INFORMATION

Brand name

Prolastin-C

Active ingredient

Alpha-1-proteinase inhibitor

Schedule

S4

 

Name of the medicine

Alpha-1-proteinase inhibitor (human).

Excipients.

Sodium Chloride, USP; Monobasic Sodium Phosphate, USP; sterile water for injection.

Description

CAS: 9041-92-3. Prolastin-C is a sterile, white to beige colored, lyophilised powder of alpha-1-proteinase inhibitor (alpha1-PI). Prolastin-C is produced from pooled human plasma using purification by polyethylene glycol (PEG) precipitation, anion exchange chromatography, and cation exchange chromatography.
The specific activity of Prolastin-C is ≥ 0.7 mg functional alpha1-PI per mg of total protein. Prolastin-C has a purity of ≥ 90% alpha1-PI (alpha1-PI protein/ total protein). Each vial contains approximately 1,000 mg of functionally active alpha1-PI as determined by capacity to neutralize porcine pancreatic elastase. When reconstituted with 20 mL of sterile water for injection, Prolastin-C has a pH of 6.6-7.4, a sodium content of 100-210 mM, a chloride content of 60-180 mM and a sodium phosphate content of 13-25 mM.
Prolastin-C contains no preservative and must be administered by the intravenous route.
Prolastin-C is prepared from pooled human plasma collected from donors in the USA.
The Prolastin-C manufacturing process includes several steps (cold ethanol fractionation, PEG precipitation, and depth filtration) that are important for purifying alpha1-PI as well as removing potential virus contaminants. Two additional steps, solvent/ detergent treatment and 15 nanometer virus removal nanofiltration, are included in the process as dedicated pathogen reduction steps. The solvent/ detergent treatment step effectively inactivates enveloped viruses (such as human immunodeficiency virus type 1 (HIV-1), vesicular stomatitis virus (VSV), hepatitis B virus (HBV), hepatitis C virus (HCV), and West Nile virus (WNV)). The 15 nanometer virus removal nanofiltration step has been implemented to reduce the risk of transmission of enveloped and nonenveloped viruses as small as 18 nanometer.
Additionally, the manufacturing process was investigated for its capacity to decrease the infectivity of an experimental agent of transmissible spongiform encephalopathy (TSE) considered as a model for the variant Creutzfeldt-Jakob disease (vCJD) and Creutzfeldt-Jakob disease (CJD) agents. Studies of the Prolastin-C manufacturing process demonstrate that a minimum of 6 log10 reduction of TSE infectivity is achieved. These studies provide reasonable assurance that low levels of vCJD/CJD agent infectivity, if present in the starting material, would be removed.

Pharmacology

Congenital alpha-1-proteinase inhibitor deficiency.

Alpha1-PI deficiency (alpha-1 antitrypsin deficiency, AAT deficiency) is an autosomal, codominant, hereditary disorder characterized by low serum and lung levels of alpha1-PI. Smoking is an important risk factor for the development of emphysema in patients with alpha1-PI deficiency. Because emphysema affects many, but not all individuals with the more severe genetic variants of alpha1-PI deficiency, augmentation therapy with alpha-1-proteinase inhibitor (human) is indicated only in patients with severe alpha1-PI deficiency who have clinically evident emphysema.
Only some alpha1-PI alleles are associated with clinically apparent alpha1-PI deficiency. Approximately 95% of all severely alpha1-PI deficient patients are homozygous for the PiZ allele. Individuals with the PiZZ variant typically have serum alpha1-PI levels less than 35% of the average normal level. Individuals with the Pi(null)(null) variant have undetectable alpha1-PI protein in their serum. Individuals with these low serum alpha1-PI levels, i.e. less than 11 microM, have a markedly increased risk for developing emphysema over their lifetimes. In addition, PiSZ individuals, whose serum alpha1-PI levels range from approximately 9 to 23 microM, are considered to have moderately increased risk for developing emphysema, regardless of whether their serum alpha1-PI levels are above or below 11 microM.
Augmenting the levels of functional protease inhibitor by intravenous infusion is an approach to therapy for patients with alpha1-PI deficiency. The intended theoretical goal is to provide protection to the lower respiratory tract by correcting the imbalance between neutrophil elastase and protease inhibitors. The maintenance of blood serum levels of alpha1-PI (antigenically measured) above 11 microM has been historically postulated to provide therapeutically relevant antineutrophil elastase protection. Individuals with severe alpha1-PI deficiency have been shown to have increased neutrophil and neutrophil elastase concentrations in lung epithelial lining fluid compared to normal PiMM individuals, and some PiSZ individuals with alpha1-PI above 11 microM have emphysema attributed to alpha1-PI deficiency.

Mechanism of action.

The pathogenesis of emphysema is understood to evolve as described in the ‘protease-antiprotease imbalance’ model. Alpha1-PI is understood to be the primary antiprotease in the lower respiratory tract, where it inhibits neutrophil elastase. Normal healthy individuals produce sufficient alpha1-PI to control the neutrophil elastase produced by activated neutrophils and are thus able to prevent inappropriate proteolysis of the lung tissue by neutrophil elastase. Conditions that increase neutrophil accumulation and activation in the lung, such as respiratory infection and smoking, will in turn increase levels of neutrophil elastase. However, individuals who are severely deficient in endogenous alpha1-PI are unable to maintain an appropriate antiprotease defence, and, in addition, they have been shown to have increased lung epithelial lining fluid neutrophil and neutrophil elastase concentrations. Because of these factors, many (but not all) individuals who are severely deficient in endogenous alpha1-PI are subject to more rapid proteolysis of the alveolar walls leading to chronic lung disease. Prolastin-C serves as alpha1-PI augmentation therapy in the patient population with severe alpha1-PI deficiency and emphysema, acting to increase and maintain serum and lung epithelial lining fluid levels of alpha1-PI.

Pharmacodynamics.

In clinical studies, patients received Prolastin replacement therapy, 60 mg/kg bodyweight, once weekly for up to 26 weeks (average 24 weeks of therapy). With this schedule of replacement therapy, blood levels of alpha1-PI were maintained above 80 mg/dL (based on the commercial standards for alpha1-PI immunologic assay). Chronic augmentation therapy results in significantly increased levels of alpha1-PI and functional antineutrophil elastase capacity in the epithelial lining fluid of the lower respiratory tract of the lung, as compared to levels prior to commencing augmentation therapy with Prolastin.

Pharmacokinetics.

The pharmacokinetic (PK) profile of Prolastin-C was evaluated in a randomised, double blind, crossover clinical trial comparing Prolastin-C to Prolastin conducted in 24 adult subjects age 40 to 72 with severe alpha1-PI deficiency. Ten subjects were male and 14 subjects were female. Twelve subjects were randomised to each treatment sequence. All but one subject had the PiZZ genotype and the remaining subject had PiSZ. All subjects had received prior alpha1-PI therapy with Prolastin for at least 1 month.
Study subjects were randomly assigned to receive either 60 mg/kg bodyweight of functional Prolastin-C or Prolastin weekly by intravenous infusion during the first 8 week treatment period. Following the last dose in the first 8 week treatment period, subjects underwent serial blood sampling for PK analysis and then crossed over to the alternate treatment for the second 8 week treatment period. Following the last treatment in the second 8 week treatment period, subjects underwent serial blood sampling for PK analysis. In addition, blood samples were drawn for trough levels before infusion at weeks 6, 7, and 8, as well as before infusion at weeks 14, 15, and 16.
In the 8 week open label treatment phase that followed the crossover period, all subjects received 60 mg/kg bodyweight of functional Prolastin-C.
The pharmacokinetic parameters of alpha1-PI in plasma, based on functional activity assays, showed comparability between Prolastin-C treatment and Prolastin treatment, see Table 1.
The key pharmacokinetic parameter was the area under the plasma concentration time curve (AUC0-7days) following 8 weeks of treatment with Prolastin-C or Prolastin. The 90% confidence interval (0.97-1.09) for the ratio of AUC0-7days for Prolastin-C and Prolastin indicated that the 2 products are pharmacokinetically equivalent. Figure 1 shows the concentration (functional activity) vs. time curves of alpha1-PI after intravenous administration of Prolastin-C and Prolastin.
Trough levels measured during the crossover PK study via an antigenic content assay showed Prolastin-C treatment resulted in a mean trough of 16.9 ± 2.3 microM and Prolastin resulted in a mean trough of 16.7 ± 2.7 microM. Using the functional activity assay, Prolastin-C resulted in a mean trough of 11.8 ± 2.2 microM and Prolastin resulted in a mean trough of 11.0 ± 2.2 microM.

Clinical Trials

Efficacy.

A randomised, placebo controlled study, EXAcerbations and CT scan as Lung Endpoints (EXACTLE), was conducted with the precursor product, Prolastin to assess the loss of lung tissue and effect of augmentation therapy in AAT deficiency using computed tomography (CT) densitometry. In total, 77 patients with AAT deficiency (three centers) were randomised to receive weekly infusions of either 60 mg/kg human AAT (Prolastin) or placebo (2% albumin) over 2 to 2.5 years. CT was performed at baseline, 12, 24, and 30 months. The primary endpoint was the 15th percentile of whole lung density assessed by CT scan. Four prospectively defined methods were used for statistical analyses. A trend of reduced loss of lung tissue in patients with AAT deficiency receiving augmentation therapy versus those on placebo was demonstrated when data were analyzed via any of the four methods. While this trial was not powered to achieve statistical significance, the four analyses resulted in p-values between 0.049 and 0.084. Prolastin was also found to modify exacerbations. The duration of the exacerbation in the Prolastin group was about 10% shorter than the placebo group and there were significantly fewer severe exacerbations in the Prolastin group. Other lung function parameters (FEV1, KCO, DLCO SVC, TLC, IVC, ERV, FRC and ERV/FRC) consistently reflected a similar deterioration of lung function in both treatment groups. The quality of life as determined with the percentage score of the SGRQ remained on average unchanged.
The clinical efficacy of Prolastin-C or any alpha1-PI product in influencing the course of pulmonary emphysema or pulmonary exacerbations has not been demonstrated in adequately powered, randomised, controlled clinical trials.

Indications

Prolastin-C is an alpha-1-proteinase inhibitor (human, alpha1-PI) indicated to increase serum alpha1-PI levels in adults with congenital deficiency of alpha-1 antitrypsin and with clinically significant emphysema (FEV1 < 80%).
The data for clinical efficacy of Prolastin-C is derived from changes in the biomarkers alpha1-antiprotease level and CT lung density. Efficacy on FEV1 or patient relevant endpoints such as quality of life or pulmonary exacerbations has not been established in randomised clinical trials.
Clinical trials have only included patients who were not smoking.

Contraindications

Prolastin-C is contraindicated in IgA deficient patients with antibodies against IgA, due to the risk of severe hypersensitivity.

Precautions

Hypersensitivity reactions.

Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, promptly stop the infusion and begin appropriate therapy.
Prolastin-C may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Prolastin-C is contraindicated in patients with antibodies against IgA.

Transmissible infectious agents.

Because Prolastin-C 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.
Discuss the risks and benefits of this product with the patient, before prescribing or administering it to a patient. Report all infections thought by a physician possibly to have been transmitted by this product to Grifols Australia Pty Ltd 1800 339 479.

Effects on fertility.

No studies have been conducted on the effect of Prolastin-C on fertility.

Use in pregnancy.

(Category B2)
Animal reproduction studies have not been conducted with Prolastin-C. It is not known whether Prolastin-C can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Prolastin-C should be given to a pregnant woman only if clearly needed.

Use in lactation.

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

Paediatric use.

Safety and effectiveness in the paediatric population have not been established.

Use in the elderly.

Clinical studies with Prolastin-C did not contain sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. As for all patients, dosing for geriatric patients should be appropriate to their overall situation.

Genotoxicity.

Genotoxicity studies have not been conducted with Prolastin-C.

Carcinogenicity.

Carcinogenicity studies have not been conducted with Prolastin-C.

Effects on laboratory tests.

Alpha-1-proteinase inhibitor is a normal constituent of human blood plasma so no specific effects on laboratory testing should be anticipated.

Interactions

None known.

Adverse Effects

Clinical studies.

The most serious adverse reaction observed during clinical studies with Prolastin-C was an abdominal and extremity rash in one subject. The rash resolved subsequent to outpatient treatment with antihistamines and steroids. Two instances of a less severe, pruritic abdominal rash were observed upon rechallenge despite continued antihistamine and steroid treatment, which led to withdrawal of the subject from the trial.
The most common drug related adverse reactions observed at a rate of ≥ 1% in subjects receiving Prolastin-C were chills, malaise, headache, rash, hot flush and pruritus.
Because clinical studies are conducted under widely varying conditions, adverse event rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.
Two separate clinical studies were conducted with Prolastin-C: (1) a 20 week, open label, single arm safety study in 38 subjects, and (2) a 16 week, randomised, double blind, crossover pharmacokinetic comparability study vs. Prolastin in 24 subjects, followed by an 8 week open label treatment with Prolastin-C. Thus, 62 subjects were exposed to Prolastin-C in clinical trials.
Adverse reactions considered drug related by the investigators occurring in 1.6% of subjects (one subject each) treated with Prolastin-C were malaise, headache, rash, hot flush, and pruritus. Drug related chills occurred in 3.2% (2 subjects) of Prolastin-C subjects.
Adverse events occurring irrespective of causality in ≥ 5% of subjects in the first 8 weeks of treatment are shown in Table 2. Adverse events which occurred in the first 8 weeks of treatment are shown in the table in order to control for the differing treatment durations of the safety and PK studies (20 weeks vs. two 8 week periods).
Table 3 displays the overall adverse event rate (> 0.5%), irrespective of causality, as a percentage of infusions received.
Table 4 displays the overall rates of adverse events (≥ 5%), in the first eight weeks of treatment, that began during or within 72 hours of the end of an infusion of Prolastin-C or Prolastin.
Ten exacerbations of chronic obstructive pulmonary disease were reported by 8 subjects in the 24 week pharmacokinetic crossover study. During the 16 week double blind crossover phase, 4 subjects (17%) had a total of 4 exacerbations during Prolastin-C treatment and 4 subjects (17%) had a total of 4 exacerbations during Prolastin treatment. Two additional exacerbations in 2 subjects (8%) occurred during the 8 week open label treatment period with Prolastin-C. The overall rate of pulmonary exacerbations during treatment with either product was 0.9 exacerbations per subject year.

Postmarketing surveillance.

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.
The reactions which have been chosen for inclusion due to their seriousness, frequency of reporting, possible causal connection to Prolastin-C, or a combination of these factors, are the following.

General.

Chest discomfort/ chest pain, chills, malaise, influenza-like illness, fatigue.

Nervous system.

Dizziness, headache.

Skin and subcutaneous system.

Pruritus and rash including urticaria.

Respiratory system.

Dyspnea.

Immune system.

Hypersensitivity including anaphylactoid/ anaphylactic reactions.

Cardiac.

Tachycardia.

Dosage and Administration

For intravenous use only.
Treatment must be initiated and monitored by a respiratory physician, and should be in conjunction with other pharmacological and nonpharmacological therapies.
To be eligible for treatment, patients must be diagnosed with alpha-1 antitrypsin deficiency on the basis of genotype, as well as have levels of alpha-1 antitrypsin < 11 microM/L, and clinical symptoms of emphysema.

Dosage.

The recommended dose of Prolastin-C is 60 mg/kg bodyweight administered intravenously once weekly.
Dose ranging studies using efficacy endpoints have not been performed with any alpha-1-proteinase inhibitor product.
The label on each vial of Prolastin-C shows the amount of functionally active alpha1-PI in milligrams (as determined by the capacity to neutralize porcine pancreatic elastase).

Reconstitution.

1. Allow unopened Prolastin-C and diluent vials to warm up to room temperature before reconstitution.
2. Remove the plastic flip tops from each vial.
3. Swab the exposed stopper surfaces with alcohol and allow to dry.
4. Remove the plastic cover from the short end of the transfer needle. Insert the exposed end of the needle through the center of the stopper in the diluent vial.
5. Remove the cover at the other end of the transfer needle by twisting it carefully.
6. Invert the diluent vial and insert the attached needle into the Prolastin-C vial at a 45° angle. This will direct the stream of diluent against the wall of the product vial and minimize foaming. The vacuum will draw the diluent into the Prolastin-C vial.
7. Remove the diluent vial and transfer needle.
8. Immediately after adding the diluent, swirl vigorously for 10 to 15 seconds to thoroughly break up cake, then swirl continuously until the powder is completely dissolved. Some foaming will occur, but does not affect the quality of the product.
9. Inspect the reconstituted Prolastin-C visually for particulate matter and discoloration prior to pooling. A few small particles may remain after reconstitution. If particles are visible, remove by passage through a sterile filter, such as a 15 micron filter used for administering blood products (not supplied).
10. Pool reconstituted Prolastin-C from several vials into an empty, sterile intravenous solution container using aseptic technique. Use the sterile filter needle provided for this purpose.
11. Keep reconstituted solution at room temperature for administration within three hours.

Administration.

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.
Infuse Prolastin-C intravenously at 0.08 mL/kg/min as determined by patient response and comfort. The recommended dosage of 60 mg/kg takes approximately 15 minutes to infuse.
Infuse Prolastin-C separately, without mixing with other agents or diluting solutions. Administer within 3 hours of reconstitution.

Overdosage

To date, there have been no reported cases of overdose for alpha-1-proteinase inhibitor (human). No data are available concerning overdose in humans.
For information on the management of overdose, contact the Poisons Information Centre on 131 126 (Australia).

Presentation

Powder for injection, 1000 mg (white to beige, sterile, lyophilised, nonpyrogenic, preservative free): 1’s (composite pack containing glass vial, 20 mL diluent (sterile water for injection in glass vial), 1 sterile filter needle and 1 color coded transfer needle in carton).

Storage

Store at or below 25°C.
Do not use after the expiration date on its label.

Special precautions for storage.

Do not freeze as breakage of the diluent vial might occur.

Poison Schedule

S4.