Vademecum

Vademecum

DORNASA
Nota importante

DESCRIPCION

La a-dornasa es una enzima que se administra por inhalación para ayudar a eliminar las secreciones bronquiales en los pacientes con fibrosis cística. La a-dornasa es una desoxiribonucleasa humana, producida por ingenieria genética en células de ovario de hamster chino. La a-dornasa es la primera enzima DNAasa recombinante utilizada en el tratamiento de la fibrosis cística, aunque una DNAasa de origen pancreático bovino ha sido utilizada con éxito en la década de los 60

Mecanismo de acción: Dornase alfa hydrolyzes extracellular DNA. The exact mechanism of hydrolysis is unknown. There is no effect on intracellular DNA.[380] In CF patients, dornase alfa cleaves extracellular DNA which is present in increased amounts in pulmonary secretions due to the degeneration of leukocytes, bacteria, and tissue. In vitro studies show that by cleaving extracellular DNA, dornase alfa decreases the viscosity of the sputum which then improves mucociliary clearance of sputum.[381] [382] Also, in these patients, dornase alfa reduces the incidence of recurrent bacterial infections. Clinical trials report that patients given dornase alfa have an increase in general perception of well-being and a decreased perception of dyspnea, frequency of cough and chest congestion.[383] [384] Beneficial effects subside within several days after discontinuation. Pharmacokinetics: Dornase alfa is administered by inhalation. Administration of a usual dose to cystic fibrosis patients results in sputum concentrations of approximately 3 µg/ml within 15 minutes. Mean sputum concentrations declined to an average of 0.6 µg/ml 2 hours following inhalation. Following chronic administration, no accumulation of serum DNase occurs. Other pharmacokinetic parameters for dornase alfa are not available.

Tratamiento de la fibrosis cística en combinación con otros tratamientos estándar:

Administración por inhalación:

For the management of cystic fibrosis in conjunction with standard therapies, to improve pulmonary function: Inhalation dosage: Adults, children, and infants >= 3 months: 2.5 mg via oral inhalation once daily using a recommended nebulizer (see Administration above). Some patients may benefit from 2.5 mg via oral inhalation twice daily. In patients with an FVC >= 40% of predicted, daily administration of dornase alfa has been shown to reduce the risk of respiratory tract infections requiring parenteral antibiotics. Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Administration Nebulization Administration �The manufacturer recommends that one of the following nebulizers and compressors be used to deliver dornase alfa (Pulmozyme®): 1) the disposable jet nebulizer Hudson T Up-draft II in conjunction with a Pulmo-Aide compressor. 2) the disposable jet nebulizer Marquest Acorn II in conjunction with a Pulmo-Aide compressor. 3) the reusable PARI LC Jet nebulizer in conjunction with the PARI PRONEB compressor. 4) the PARI BABY� reusable nebulizer can be used in young children unable to inhale or exhale orally throughout the treatment period; the PARI BABY� nebulizer is identical to the PARI LC Jet system except the mouthpiece is replaced by a tight fitting facemask connected to an elbow piece. These nebulizer systems are recommended because safety and efficacy have been demonstrated with these machines and there is no clinical data to support the use of dornase alfa (Pulmozyme®) with other nebulizer systems. �In order to avoid adverse physicochemical and/or functional changes, dornase alfa (Pulmozyme®) should not be diluted or mixed with other drugs in the nebulizer. Oral inhalation via nebulization: �Empty entire contents of the single-use ampul into the nebulizer cup and attach cup to the nebulizer according to the manufacturer's instruction. Discard any unused portions because the inhalation solution contains no preservatives. �Instruct patient on proper inhalation technique (see manufacturer's labeling). Breathe through the mouth; do not breathe through the nose. A nose clip may be used in patients unable to breathe correctly. Continue therapy until nebulizer cup is empty or the nebulizer stops producing a mist.

CONTRAINDICACIONES

Dornase alfa is contraindicated in patients who have previously demonstrated hamster protein hypersensitivity. Dornase alfa is manufactured using Chinese hamster ovary cells. No contraindications other than hamster protein hypersensitivity or hypersensitivity to the product or its ingredients are known. Dornase alfa should be used in conjunction with standard cystic fibrosis therapies. It is not known if dornase alfa is distributed into breast milk. Dornase alfa should be used with caution in women who are breast-feeding. Dornase alfa is classified as pregnancy category B. Animal studies have revealed no evidence of impaired fertility, harm to the fetus, or effects on development of the fetus. Adequate studies in humans have not been conducted; therefore, dornase alfa should be used during pregnancy only when clearly needed. Because of the limited experience with administration of dornase alfa to children < 5 years, the risks and benefits of use should be considered carefully prior to initiation of therapy.

No clinically-significant drug interactions are noted for this drug.

Adverse Reactions According to manufacturer product literature, adverse reactions reported below are from a large, randomized, placebo-controlled clinical trial involving over 600 patients receiving dornase alfa once or twice daily. Adverse reactions that occurred more frequently in dornase alfa-treated patients than in placebo-treated patients included chest pain (18�25% vs 16�23%), conjunctivitis (1�5% vs 0�2%), pharyngitis (32�40% vs 28�33%), laryngitis (3�4% vs 1%), hoarseness (12�18% vs 6�7%), and maculopapular rash (3�12% vs 1�7%). In patients with advanced cystic fibrosis, additional adverse events reported more frequently in dornase alfa-treated patients than in placebo-treated patients included rhinitis (20% vs 24%), fever (32% vs 28%), and serious dyspnea (17% vs 12%); total reports of dyspnea (regardless of severity or seriousness) were similar among treatment and placebo groups. In patients with mild to moderate cystic fibrosis (FVC > 40% of predicted), the incidence of adverse reactions was slightly greater in patients receiving dornase alfa twice daily than in those receiving once daily treatment. Adverse reactions that appear more common in younger children (aged 3 months to < 5 years) than in older children (aged 5 to <= 10 years) include cough (45% vs 30%), rhinitis (35% vs 27%), and maculopapular rash (6% vs 0%). Other adverse reactions observed at similar rates in both doranse alfa and placebo treated patients include abdominal pain, asthenia, flu syndrome, malaise, sepsis, intestinal obstruction, gall bladder disease, liver disease, pancreatic disease, diabetes mellitus, hypoxia, weight loss, apnea, bronchiectasis, bronchitis, sputum changes, cough increase, hemoptysis, lung function decrease, nasal polyps, pneumonia, pneumothorax, sinusitis, and wheeze.

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REFERENCIAS

  • Armstrong JB, White JC. Liquefaction of viscous purulent exudates by deoxyribonuclease. Lancet 1950;i:739�45.
  • Zahm JM, de Bentzmann S, Deneuville E, et al. Recombinant human DNase I improves the transport of cystic fibrosis respiratory mucus ex vivo. Pediatr Pulmonol 1993;Suppl 9:250.
  • Tomkiewicz RP, Shak S, King M. Effects of rhDNase on cystic fibrosis sputum viscoelasticity in vitro. Pediatr Pulmonol 1993;Suppl 9:251.
  • Ranasinha C, Assoufi B, Shak S, et al. Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am Rev Respir Dis 1993a;148:145�51.
  • Ramsey B for the Pulmozyme (rhDNase) Study Group. A summary of the results of the Phase III multicenter clinical trial: aerosol administration of recombinant human DNase reduces the risk of respiratory tract infections and improves pulmonary function in patients with cystic fibrosis. Pediatr Pulmonol 1993b;Suppl 9:152�3.

 

 

Monografía creada el . Equipo de redacción de IQB (Centro colaborador de La Administración Nacional de Medicamentos, alimentos y Tecnología Médica -ANMAT - Argentina).

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