Respikam^® (Solution) Instructions for Use

Marketing Authorization Holder

Kamada Ltd. (Israel)

ATC Code

B02AB02 (Alpha1-antitrypsin)

Active Substance

Alpha-1-proteinase inhibitor (Ph.Eur. European Pharmacopoeia)

Dosage Form

Respikam®

Solution for infusion 20 mg/1 ml: bottle 50 ml 1 pc. in a set with a filter needle

Dosage Form, Packaging, and Composition

Solution for infusion transparent, from colorless to yellow-green in color, may contain a small amount of sediment (suspended protein particles).

Excipients: sodium dihydrogen phosphate dihydrate, sodium chloride, water for injections.

50 ml – glass bottles (1) in a set with a filter needle (in sterile packaging made of paper and PVC) – cardboard packs.

Clinical-Pharmacological Group

Alpha1-proteinase inhibitor used for pulmonary emphysema

Pharmacotherapeutic Group

Protease inhibitor

Pharmacological Action

Respikam^® is a sterile, ready-to-use solution containing purified alpha1-proteinase inhibitor (also known as alpha1-antitrypsin (AAT)).

Respikam^® is manufactured from the plasma of healthy humans using ion-exchange chromatography. To prevent the risk of transmission of infectious agents, each unit of human plasma used for the production of the drug is tested for human immunodeficiency virus (HIV), antibodies to hepatitis C (anti-HCV), hepatitis B surface antigen (HBsAg), and a serological test for syphilis is also performed.

Respikam^® has a therapeutic effect in AAT deficiency – a chronic hereditary, autosomal recessive disease characterized by the development of severe, slowly progressive panacinar pulmonary emphysema, most often observed in the third to fourth decade of life. It is assumed that the development of this pathological condition is due to an imbalance between elastase (an enzyme capable of destroying tissue elastin and produced mainly by neutrophils in the lower respiratory tract) and AAT – the main inhibitor of elastase. As a result of prolonged exposure to elastase, tissue elastin is destroyed and pulmonary emphysema develops. Approximately 10% of newborns with AAT deficiency have giant cell hepatitis with cholestatic jaundice. In adults, AAT deficiency may be accompanied by liver cirrhosis.

AAT deficiency is a genetic pathology at the PI gene locus, which was found on chromosome 14q32.1. The concentration of AAT in blood plasma associated with the PI type of homozygous inheritance is usually in the range of 12-18% of normal, and heterozygous inheritance is approximately 35% of normal. Many studies of the efficacy of replacement therapy were based on maintaining the AAT concentration in human blood plasma >80 mg/dL. This concentration has been found to be sufficient to prevent the development of pulmonary emphysema in such patients.

Pharmacokinetics

When Respikam^® was infused once a week at a dose of 60 mg/kg body weight in 21 patients, the mean AAT concentration was 126 mg/dL (before treatment – 30 mg/dL). Numerous studies of the efficacy of replacement therapy have shown that this concentration is sufficient to prevent the development of pulmonary emphysema in patients with congenital AAT deficiency.

During the study, it was found that in the first hours after infusion, the maximum plasma concentration is 280 mg/dL with a rapid decrease during the first 2 days, and a gradual subsequent decrease over 7 days. The half-life of the alpha1-proteinase inhibitor was 4.5 days. During the 2-year study, it did not change, indicating the absence of antibody formation in response to AAT administration.

Indications

• Congenital deficiency of alpha1-proteinase inhibitor in patients with a clinical picture of panacinar pulmonary emphysema.

For long-term replacement therapy only in patients with phenotypes PiZZ, PiZ(null) or Pi(null)(null).

ICD codes

Dosage Regimen

The drug is intended for intravenous administration only.

Adults

The recommended dose of Respikam^® for long-term replacement therapy is 60 mg per kilogram of body weight once a week intravenously by drip at a rate of 0.08 ml/kg/min or faster. The duration of Respikam^® infusion should not exceed 30 minutes. Observing aseptic rules, the required dose of the drug is drawn into a syringe from the vial using a special filter needle (supplied with the drug). After this, the filter needle is removed and replaced with a needle intended for injections. Then the dose is transferred to an appropriate plastic container (plastic bag or vial). The drug is infused using a system intended for intravenous drip administration of solutions (infusion set).

Parenteral medicinal products should be inspected visually for particulate matter and clarity of the solution prior to administration.

Respikam^® should be used after the drug’s temperature has reached room temperature.

The duration of the course is determined by the doctor.

Adverse Reactions

Respikam^® at a dose of 60 mg/kg per week is well tolerated. During the study, there were no reports of serious adverse events or fatalities. No deviations from baseline values of the main indicators of the body’s condition or laboratory parameters were identified. No changes from baseline values on the electrocardiogram (ECG) were detected. During the period of the clinical study and for 6 months after it, no changes in virological parameters were found.

When studying the safety of treatment with Respikam^® in 18 patients, 22 cases of side effects were identified, of which only 3 could be considered as possibly related to the use of Respikam^® (headache, erythema and dysgeusia) and one as probably related (hyperthermia) to its treatment.

Since alpha 1-proteinase inhibitor drugs entered the market, there have been periodic reports of other cold-like symptoms, allergy-like reactions, chills, shortness of breath, rash, tachycardia and, rarely, decreased blood pressure. Rare cases of a short-term increase in blood pressure accompanied by chest pain have also been recorded.

Contraindications

• Selective immunoglobulin A (IgA) deficiency with the presence of antibodies to IgA;
• Hypersensitivity to the components of the drug.

The safety and efficacy of the drug in children have not been established. Use in children is contraindicated.

Use in Pregnancy and Lactation

To date, there is no information on how Respikam^® affects the intrauterine development of the fetus or the reproductive function of the female body.

It is not known whether Respikam^® passes into breast milk. Therefore, alpha 1-proteinase inhibitor can be prescribed by a doctor during pregnancy and breastfeeding only in cases of acute necessity, when the expected benefit to the mother outweighs the possible risk to the fetus or child.

Pediatric Use

The safety and efficacy of the drug in children have not been established. Use in children is contraindicated.

Special Precautions

The “threshold” concentration of alpha 1-proteinase inhibitor in blood plasma, designed to provide sufficient anti-elastase action in the lungs of patients with alpha 1-antitrypsin deficiency, is 80 mg/dL (this value is based on data obtained using a standard immunological assay for the content of alpha 1-proteinase inhibitor). Despite the inactivation and/or elimination of viral pathogens during the production of Respikam^®, the presence of an unknown infectious agent in it cannot be completely excluded. Patients receiving infusions of blood or plasma products may develop signs and/or symptoms of a viral disease, such as hepatitis C. Before prescribing the drug, the doctor must weigh the risks and benefits. An increase in plasma volume after infusion of Respikam^® is possible, which should be taken into account in patients with increased circulating fluid volume.

Reuse of drug residues after infusion is not allowed.

Unused drug vials that have been taken out of the refrigerator should be returned to the refrigerator for storage within 6 hours. If the drug vial has been kept at room temperature (25°C (77°F)) for more than 48 hours, the drug is considered expired and is not allowed for further use.

Effect on the ability to drive vehicles and operate machinery

The effect of the drug on the performance of potentially hazardous activities requiring increased concentration and speed of psychomotor reactions has not been established.

Overdose

No cases of drug overdose have been reported to date. There is no antidote for the drug.

Drug Interactions

Respikam^® should not be mixed with other medicinal products.

Storage Conditions

Store at a temperature of 2 to 8°C (46.4°F). Do not freeze. Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.