Pentamidine
From Free net encyclopedia
Pentamidine isethionate is an antiparasitical/antiprotozoal drug primarily given for prevention and treatment of Pneumocystis jiroveci pneumonia, also formerly known as Pneunocystis carinii pneumonia (PCP), a type of pneumonia often seen in patients with HIV infection. PCP is considered an 'opportunistical infection', endagering only immunecompromised patients such as those with HIV/AIDS-infection. The mortality of untreated PCP is very high. Additionally, Pentamidine has good clinical activity against the parasites causing Leishmaniasis. Sleeping sickness caused by different strains of Trypanosoma is another indication. The exact nature of its antiprotozoal action is unknown. The drug has also activity against candida albicans in clinically relevant concentrations. In the US Pentamidine is currently designated an orphan drug by the FDA.
Contents |
Treatment of acute PCP
In the acute treatment of PCP Pentamidine is considered equally or slightly less active compared to co-trimoxazole (brand names Bactrim, Septrin, or Septra). Clinical evidence suggests that Pentamidine is often better tolerated than co-trimoxazole because a high dose of co-trimoxazol is needed, which is associated with a high incidence and severity of side effects (hepatitis, bone-marrow-damage, renal-damage, and life threatening skin disease (Lyell-syndrome)). Moreover, many patients are or become hypersensitive to co-trimoxazole. For treatment of PCP, 4mg of Pentamidine per kg of body weight is given intravenously once daily for 14 to 21 days. Treatment exceeding 21 days may be necessary but associated with increased toxicity. I.M.-Injection is not recommended. The effect of Pentamidine often becomes evident within the first 2 days of treatment as defeverescence and improvement of respiratory function. In any case, improvements of X-Ray studies occur within 6 to 8 days, provided therapy is successful. Pentamidine therapy cures 50 to 70% of all patients treated.
Primary and Secondary Prophylaxis of PCP
Primary prophylaxis means that so far no PCP has been diagnostized. Secondary prophylaxis aims to prevent further PCP. For both forms of prophylaxis an aerosolized formulation given by nebulizer once monthly in a dose of 300mg exists. In primary prophylaxis this reduces the longterm likelihood of PCP by 70% compared to no prophylaxis.
Other Infections
For other indications such as leishmaniasis or sleeping sickness special treatment schedules developed by WHO or CDC exist.
Contraindications
- None in PCP patients, in whom a proper diagnosis has been made
Side effects
Pentamidine causes allergic and toxic side effects, which in part depend on daily and/or cumulative dose:
- Kidney : Twentyfive (25) Per Cent develop signs of nephrotoxicity ranging from mild, asymptomatic azotemia (increased serum kreatinine and urea) to irreversible renal failure. Ample fluids or intravenous hydration may prevent some nephrotoxicity.
- Cardiovascular : Hypotension, which may be severe, severe or fatal arrhyhmias and heart failure are quite frequent.
- GI : Nausea, vomiting, gastrointestinal discomfort, diarrhea, unpleasant taste
- Pancreas : Hypoglycemia that requires symptomatic treatment is frequently seen. On the other hand Pentamidine may cause or worsen Diabetes mellitus.
- Liver : Elevated liver enzymes are associated with the intravenous use of Pentamidine. Hepatomegaly and hepatitis have been encountered with longterm prophylactic use of Pentamidine inhalation.
- Skin : Severe local reactions after extravasculation of intravenous solutions or following i.m.-treatment have been seen. Pentamidine itself may cause rash or rarely Steven-Johnson- or Lyell-Syndrome.
- Blood : Pentamidine frequently causes leucopenia and less often thrombopenia, which may cause symptomatic bleeding. Some cases of anemia, possibly related to folic acid deficiency, have been described.
- Neurological : Dizziness, drowsiness, neuralgia, confusion, hallucinations, seizures and other central side effects are reported.
- Respiratory Tract : Cough and bronchospasm, most frequently seen with inhalation.
- Others : Eye-discomfort, conjunctivitis, throat irritation, splenomegaly, Herxheimer reaction, electrolyt imbalances (e.g. hypocalcemia).
Drug Interactions
The additional or sequential use of other nephrotoxic drugs like aminoglycosids, amphotericin B, capreomycin, colistin, polymyxin B, vancomycin, foscarnet, cisplatin or methoxyfluran should be closely monitored or whenever possible completely avoided.
Brand Names and Dose Forms
- For oral inhalation : NebuPent 300mg Nebulizer
- For parenteral treatment : Pentacrinat, Pentam 300, and Pentamidine isethionate for injection (Abbot); all containing 300mg of Pentamidine
External references
- AHFS Databasefr:Pentamidine