Pentamidine Isethionate (4 brand names, 2 dosage forms, 2 routes)
Available dosage forms: INJECTABLE, FOR SOLUTION.
Routes of administration: INJECTION, INHALATION.
Brand Names
- NEBUPENT
- PENTACARINAT
- PENTAM
- PENTAMIDINE ISETHIONATE
Indications and Usage
Pentamidine Isethionate is indicated for the prevention of Pneumocystis jiroveci pneumonia (PJP) in high-risk, HIV-infected patients defined by one or both of the following criteria: i. a history of one or more episodes of PJP ii. a peripheral CD4+ (T4 helper/inducer) lymphocyte count less than or equal to 200/mm3. These indications are based on the results of an 18-month randomized, dose-response trial in high risk HIV-infected patients and on existing epidemiological data from natural history studies. The patient population of the controlled trial consisted of 408 patients, 237 of whom had a history of one or more episodes of PJP. The remaining patients without a history of PJP included 55 patients with Kaposi’s sarcoma and 116 patients with other AIDS diagnoses, ARC or asymptomatic HIV infection. Patients were randomly assigned to receive Pentamidine Isethionate via the Respirgard® II nebulizer at one of the following three doses: 30 mg every two weeks (n=135), 150 mg every two weeks (n=134) or 300 mg every four weeks (n=139). The results of the trial demonstrated a significant protective effect (p<0.01) against PJP with the 300 mg every four week dosage regimen compared to the 30 mg every two week dosage regimen. The 300 mg dose regimen reduced the risk of developing PJP by 50 to 70% compared to the 30 mg regimen. A total of 293 patients (72% of all patients) also received zidovudine at some time during the trial. The analysis of the data demonstrated the efficacy of the 300 mg dose even after adjusting for the effect of zidovudine. The results of the trial further demonstrate that the dose and frequency of dosing are important to the efficacy of Pentamidine Isethionate prophylaxis in that multiple analyses consistently demonstrated a trend toward greater efficacy with 300 mg every four weeks as compared to 150 mg every two weeks. No dose-response was observed for reduction in overall mortality; however, mortality from PJP was low in all three dosage groups.
Dosage and Administration
IMPORTANT: PENTAMIDINE ISETHIONATE MUST BE DISSOLVED ONLY IN STERILE WATER FOR INJECTION, USP. DO NOT USE SALINE SOLUTION FOR RECONSTITUTION BECAUSE THE DRUG WILL PRECIPITATE. DO NOT MIX THE Pentamidine Isethionate SOLUTION WITH ANY OTHER DRUGS. DO NOT USE THE RESPIRGARD® II NEBULIZER TO ADMINISTER A BRONCHODILATOR.
Contraindications
Pentamidine Isethionate is contraindicated in patients with a history of an anaphylactic reaction to inhaled or parenteral pentamidine isethionate.
Adverse Reactions
The most frequently reported unsolicited adverse events (1 to 5%) in clinical trials, regardless of their relation to Pentamidine Isethionate therapy were as follows (n=931): Body as a Whole: Night sweats. Gastrointestinal: Diarrhea and nausea. Hematologic: Anemia. Infection: Bronchitis, non-specific herpes, herpes zoster, non-specific influenza, oral Candida, pharyngitis, sinusitis, and upper respiratory tract. Nervous System: Headache. Respiratory System: Chest pain, cough, and wheezing. Special Senses: Bad taste. Adverse events of less than 1% incidence were as follows (No causal relationship to treatment has been established for these adverse events): Body as a Whole: Allergic reaction, non-specific allergy, body odor, facial edema, fever, leg edema, lethargy, low body temperature, and temperature abnormality. Cardiovascular: Cerebrovascular accident, hypotension, hypertension, palpitations, poor circulation, syncope, tachycardia, vasodilatation and vasculitis. Gastrointestinal: Abdominal cramps, abdominal pain, constipation, dry mouth, dyspepsia, gastritis, gastric ulcer, gingivitis, hiatal hernia, hypersalivation, oral ulcer/abscess, splenomegaly, and vomiting. Hematological: Eosinophilia, neutropenia, non-specific cytopenia, pancytopenia, and thrombocytopenia. Hepatic: Hepatitis, hepatomegaly, and hepatic dysfunction. Infection: Bacterial pneumonia, central venous line related sepsis, cryptococcal meningitis, cytomegalovirus (CMV) colitis, CMV retinitis, esophageal Candida, histoplasmosis, Kaposi’s sarcoma, non-specific mycoplasma, oral herpes, non-specific otitis, non-specific pharyngitis, pharyngeal herpes, non-specific serious infection, tonsillitis, tuberculosis, and viral encephalitis. Metabolic: Hyperglycemia, hypoglycemia, and hypocalcemia. Musculoskeletal: Arthralgia, gout, and myalgia. Neurological: Anxiety, confusion, depression, drowsiness, emotional lability, hallucination, hypesthesia, insomnia, memory loss, neuralgia, neuropathy, non-specific ne
Drug Interactions
While specific studies on drug interactions with Pentamidine Isethionate have not been conducted, the majority of patients in clinical trials received concomitant medications, including zidovudine, with no reported interactions. Because the nephrotoxic effects may be additive, the concomitant or sequential use of Pentamidine Isethionate and other nephrotoxic drugs such as aminoglycosides, amphotericin B, cisplatin, foscarnet, or vancomycin should be closely monitored and avoided, if possible.
Mechanism of Action
Studies suggest that the pentamidine isethionate interferes with microbial nuclear metabolism by inhibition of DNA, RNA, phospholipid and protein synthesis. However, the mode of action is not fully understood.
Overdosage
Overdosage has not been reported with Pentamidine Isethionate. The symptoms and signs of overdosage are not known. A serious overdosage, to the point of producing systemic drug levels similar to those following parenteral administration, would have the potential of producing similar types of serious systemic toxicity. (See PRECAUTIONS). Available clinical pharmacology data (see CLINICAL PHARMACOLOGY) suggest that a dose up to 40 times the recommended Pentamidine Isethionate dosage would be required to produce systemic levels similar to a single 4 mg/kg intravenous dose.