RCP: 110 chapter 13 - Pentamidine for Pneumocystis Pneumonia (PCP)

• Aerosolized antiinfective agents are used to treat or prevent respiratory infections.

Clinical Indications for Pentamidine

• Pentamidine can be administered via aerosolization.
• It can prevent Pneumocystis pneumonia (PCP) in HIV-infected patients.
  • This is for individuals with a history of PCP or a peripheral CD4+ (T4 helper cell) lymphocyte count of 200/mm³ or less.
• NebuPent is a brand name for aerosolized pentamidine medications.
• Rationale for aerosol administration: local targeted lung delivery and fewer/less severe side effects compared with systemic administration.
• Description of PCP: mammals usually infected at an early age and disease occurs with suppression of the immune system (commonly AIDS).
• PCP is also known as Pneumocystis jiroveci.

Dosage: Pentamidine

• 300 mg of Pentamidine delivered by inhalation once every 4 weeks, but a doctor may alter the dosage.
• Pentamidine is a dry powder: 300 mg/vial, reconstituted with 6 mL of sterile water, and not saline (can cause precipitation).

Administration: Pentamidine

• Administer using a Respirgard II nebulizer.
• Power with a flowrate of 5–7 L/min from a 50-psi gas source.
• Filter escaped particles to limit healthcare workers exposure.
• Nebulizer performance results in a mass median diameter (MMD) of 1–2 μm

Side Effects: Pentamidine

• Side effects of aerosol administration include:
  • Cough and bronchial irritation (36% of patients in one study).
  • Shortness of breath.
  • Bad taste (bitter or burning) of aerosol impacting in oropharynx.
  • Bronchospasm and wheezing in 11% of patients.
  • Spontaneous pneumothoraces and conjunctivitis.
  • Rash, neutropenia, and pancreatitis.
  • Renal insufficiency, dysglycemia (hypoglycemia and diabetes).
  • Digital necrosis in both feet, and appearance of extrapulmonary P. jiroveci infection.

Environmental Contamination: Pentamidine

• Nebulized pentamidine causes environmental contamination.
• There is exposure to the drug itself from exhaust aerosol.
• There is a risk of infection with tuberculosis.
• Pentamidine is not known to be teratogenic or mutagenic and has minimal carcinogenic potential.

Clinical Indications for Ribavirin

• Ribavirin is aerosolized to treat hospitalized infants who have severe lower respiratory tract infection caused by respiratory syncytial virus (RSV).
• Ribavirin is an antiviral drug active against RSV, influenza viruses, and herpes simplex virus.
• Ribavirin is a nucleoside analog, which resembles guanosine and inosine.
• It is virostatic, not virucidal, and inhibits both DNA and RNA (retrovirus) viruses.

Nature of Viral Infection

• Process of viral infection: adsorbs to cell, penetrates cell, uncoats itself, recodes cell DNA, assembles itself, and sheds from cell.
• Viruses are obligate intracellular parasites, diagnosis is based on clinical signs and requires isolating virus or demonstrating antibody titer increase.

Dosage: Ribavirin

• Administered as a 20-mg/mL solution via SPAG-2 for 12 to 18 hr/day for a minimum of 3 days, but no more than 7 days.
• Ribavirin is supplied as 6 g of powder in a 100-mL vial and has a concentration of 6 g/300 mL.

Side Effects: Ribavirin

• Pulmonary side effects include deterioration of pulmonary function and worsening of asthma or chronic obstructive disease, pneumothorax, apnea, and bacterial pneumonia.
• Cardiovascular side effects include cardiovascular instability, hypotension, cardiac arrest, and digitalis toxicity.
• Hematological side effects on blood cells have been reported with oral or parenteral administration, but not with aerosol use.
  • Reticulocytosis (excess of young erythrocytes in circulation) has been reported with aerosol use.
• Dermatological/topical side effects include rash, eyelid erythema, and conjunctivitis.

Environmental Contamination: Ribavirin

• Aerosolized ribavirin has potential for mutagenic and carcinogenic effects and its effect on fertility is uncertain.
  • It has caused testicular lesions in rats.
• Aerosolized ribavirin's effect on pregnancy is of particular concern becuase it can be teratogenic or embryocidal in animal species.

Palivizumab (Synagis)

• Palivizumab is indicated to prevent serious lower respiratory tract disease caused by RSV in children and infants at high risk.
• Safety and efficacy established for infants with BPD, premature infants (<35 weeks), and children with congenital heart disease.
• Dosage and administration: 15 mg/kg, given IM monthly in RSV season.
• Palivizumab's mechanism of action: monoclonal antibodies, which provides neutralizing and fusion-inhibiting activity; prevents viral replication.