Pentamidine: Clinical Use & Dosage

Clinical Indications for Pentamidine

• Used for the prevention of Pneumocystis pneumonia (PCP) in HIV-infected patients.
• Patients should have a history of one or more PCP episodes or a peripheral CD4+ lymphocyte count of 200/mm³ or less.
• Administration focuses on local lung delivery.
• Aerosol administration results in fewer or less severe side effects compared to systemic administration.
• PCP typically infects mammals at an early age.
• The disease is linked to immune system suppression, commonly AIDS.
• PCP is caused by Pneumocystis jiroveci.
• Typical season for RSV is October to March.

Dosage: Pentamidine

• Administer 300 mg by inhalation once every 4 weeks.
• Dosage may be altered by the treating physician.
• Administered via dry powder.
• Each vial contains 300 mg of pentamidine
• Must be reconstituted with 6 mL of sterile water.
• Saline should not be used because it can cause precipitation.

Administration: Pentamidine

• Use a Respirgard II nebulizer.
• The nebulizer should be powered by a flow rate of 5–7 L/min from a 50-psi gas source.
• Use filters for escaped particles to limit exposure to healthcare workers.
• Nebulizer has a mass median diameter (MMD) of 1–2 μm.

Side Effects: Pentamidine

• Cough and bronchial irritation occur in 36% of patients in one study.
• Shortness of breath is another side effect.
• Bad taste, either bitter or burning, results from aerosol impacting the oropharynx.
• Bronchospasm and wheezing occur in 11% of patients.
• Other side effects include spontaneous pneumothoraces, conjunctivitis, rash, neutropenia, pancreatitis, and renal insufficiency.
• Dysglycemia, including hypoglycemia and diabetes, can also occur.
• Digital necrosis in both feet has been reported.
• Appearance of extrapulmonary P. jiroveci infection is a rare side effect.

Environmental Contamination: Pentamidine

• There is environmental contamination by nebulized pentamidine.
• There is exposure to the drug itself from exhaust aerosol.
• There is a risk of infection with tuberculosis.
• It is not known to be teratogenic or mutagenic.
• Carcinogenic potential is minimal.

Clinical Indications for Ribavirin

• Used for treatment of hospitalized infants with severe lower respiratory tract infection caused by respiratory syncytial virus (RSV).
• Ribavirin is an antiviral drug.
• Ribavirin is active against RSV, influenza viruses, and Herpes simplex virus.
• Classified as a nucleoside analog.
• It resembles guanosine and inosine.
• It is virostatic and not virucidal.
• Inhibits both DNA and RNA retroviruses.

Nature of Viral Infection

• Virus adsorbs to cell
• Penetrates cell
• Uncoats itself
• Recodes cell DNA
• Assembles itself
• Sheds from cell
• Obligate intracellular parasite
• Diagnosis is usually based on clinical signs
• Requires isolating virus or demonstrating anitbody titer increase

Dosage: Ribavirin

• Administered as a 20-mg/mL solution via SPAG-2.
• Administered for 12 to 18 hours per day for a minimum of 3 days and not more than 7 days.
• Supplied as 6 g of powder in a 100-mL vial.
• Concentration of 6 g/300 mL.

Side Effects: Ribavirin

• Pulmonary: Deterioration of pulmonary function and worsening of asthma or chronic obstructive disease; pneumothorax, apnea, and bacterial pneumonia have been reported.
• Cardiovascular: Cardiovascular instability, including hypotension, cardiac arrest, and digitalis toxicity.
• Hematological: Effects on blood cells have been reported with oral or parenteral administration but not with aerosol use.
• Reticulocytosis is reported with aerosol use.
• Dermatological/topical: Rash, eyelid erythema, and conjunctivitis can occur.

Environmental Contamination: Ribavirin

• There is potential for mutagenic and carcinogenic effects.
• The effect on fertility is uncertain.
• Caused testicular lesions in rats.
• Effect on pregnancy is a concern.
• Teratogenic or embryocidal in animal species.

RSV Infection—Other Agents: Palivizumab (Synagis)

• Used for the prevention of serious lower respiratory tract disease caused by RSV in children and infants at high risk.
• Safety and efficacy are established for infants with BPD, premature infants (less than 35 weeks), and children with congenital heart disease.
• 15 mg/kg given IM monthly during RSV season.
• Mechanism of action involves monoclonal antibodies.
• Provides neutralizing and fusion-inhibiting activity to prevent viral replication.

Clinical Indications for Tobramycin

• Used for the management of chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF).
• Clinical use is for treating pulmonary infections in CF patients.
• It aims to treat or prevent early colonization with P. aeruginosa.
• Tobramycin is used to maintain present lung function or reduce the rate of deterioration.

Aerosolized Tobramycin

• Administered at 300 mg BID.
• 28 days consecutively followed by 28 days off.
• Administered as 300 mg in a 5-mL ampule.
• Must be administered with PARI LC Plus nebulizer.
• Binds irreversibly to the 30S subunit of bacterial ribosomes, blocking protein synthesis in bacteria and causing cellular death.
• Bactericidal.

General Considerations: Tobramycin

• Aerosolizing antibiotics may affect nebulizer performance.
• Consideration must be given to environmental contamination.
• Incompatibility with other drugs is also a concern.

Clinical Indications for Aztreonam

• Used to improve symptoms in CF patients with P. aeruginosa infection.
• Primarily used for pulmonary infections in CF patients.
• Improves pulmonary symptoms in CF patients colonized with P. aeruginosa.
• Not indicated for patients under 7 years old.
• Only studied in patients having a FEV1 about 25% or below 75% of predicted.

Aerosolized Aztreonam

• Must be reconstituted.
• 2-mL single-use glass vials contain 75 mg of lyophilized aztreonam.
• Must be mixed with the provided 1 mL of sterile diluent (0.17% sodium chloride).
• Comes in a 28-day kit.
• Delivered by itself using the Altera Nebulizer System.

Clinical Indications for Zanamivir

• For influenza in adults and children 5 years and older who have been symptomatic for no more than 2 days.
• It can be used off-label for treatment and prophylaxis of H1N1 influenza A (swine flu).
• Administered via DPI (Diskhaler).
• Each blister contains 5 mg delivered in two inhalations (two blisters, for a total of 10 mg).
• Taken twice a day, approximately 12 hours apart, for 5 days.
• Suitable for adults and children 5 years and older.

Inhaled Zanamivir (Cont.)

• Adverse effects include bronchospasm and deterioration of lung function in patients with underlying asthma or COPD.
• Undertreatment of bacterial infection and allergic reactions can occur
• Other adverse effects include gastrointestinal issues, respiratory symptoms, and dizziness/headache.

Inhaled Zanamivir

• Treatment with 10 mg of zanamivir twice daily resulted in approximately 1 day less to median time to improvement in symptoms compared with placebo.
• Treatment with zanamivir 30 hours or less after the onset of symptoms resulted in 3 days or less to the median time to alleviation of symptoms.
• Not generally recommended for patients with underlying airway disease.
• Not approved for prophylaxis.

Respiratory Care Assessment: Before Treatment

• Assess the patient for the presence of a disease in which the use of the agent is indicated.
• Pentamidine: risk of PCP
• Ribavirin: presence of severe RSV infection
• Tobramycin: chronic P. aeruginosa infection in CF patient
• Aztreonam: chronic P. aeruginosa infection in CF patient
• Zanamivir: acute influenza infection within two days of onset
• Assess equipment
• Initial patient assessment

General Contraindications

• Pentamidine: Bronchospasm and cough
• Ribavirin: Pregnant caregivers should avoid exposure.
• Tobramycin: Drug resistance
• Aztreonam: Drug resistance
• Zanamivir: Caution in patients with preexisting airway disease