pentamidine isetionate

Indication & Dosage	Parenteral African trypanosomiasis Adult: For early stage infection due to Trypanosomabrucei gambiense: 4 mg/kg daily or on alternate days by IM inj or IV infusion for a total of 7-10 doses. Not effective for trypanosomiasis involving CNS but 2 doses may be given in late-stage infection prior to starting treatment with eflornithine or melarsoprol. Child: 1 mth- 18 yr: 4 mg/kg daily or on alternate days by IM inj or IV infusion; total of 7-10 doses. Renal impairment: Dose adjustment may be needed. Intramuscular Leishmaniasis Adult: For visceral leishmaniasis or mucocutaneous leishmaniasis due to Leishmanis braziliensis or L. aethiopica: 4 mg/kg 3 times wkly for 5-25 wk or longer. Alternative treatment: for visceral leishmaniasis: 3-4 mg/kg on alternate days up to a max of 10 inj, may repeat course; for cutaneous leishmaniasis due to L. aethiopica or L. guyanensis: 3-4 mg/kg 1-2 times wkly until resolution of the condition; for diffuse cutaneous leishmaniasis due to L. aethiopica: 3-4 mg/kg wkly, continue for at least 4 mth after parasites are no longer detectable on skin smears. Child: 1 mth-18 yr: For visceral leishmaniasis: 3-4 mg/kg on alternate days; max: 10 inj; may repeat course if necessary. Dose to be given via deep IM inj. For cutaneous leishmaniasis: 3-4 mg/kg 1-2 times wkly until condition resolves. Renal impairment: Dose adjustment may be needed. Parenteral Pneumocystis (carinii) jiroveci pneumonia Adult: 4 mg/kg once daily for 14 days or longer, by IM inj or preferably slow IV infusion. Child: 1 mth-18 yr: 4 mg/kg once daily for at least 14 days. CrCl (ml/min) Dosage Recommendation 10-50 Administer dose every 24-36 hr. <10 Administer dose every 48 hr. Inhalation Prophylaxis of Pneumocystis(carinii) jiroveci pneumonia Adult: In HIV-positive patients: 300 mg once every 4 wk. For patients who cannot tolerate this dose: 150 mg every 2 wk. Child: 1 mth- 18 yr: 300 mg every 4 wk or 150 mg every 2 wk via suitable nebuliser. CrCl (ml/min) Dosage Recommendation 10-50 Administer dose every 24-36 hr. <10 Administer dose every 48 hr. Inhalation Mild to moderate P. (carinii) jirovecii infection Adult: 600 mg daily for 3 wk via nebulisation. Child: 1 mth-18 yr: 600 mg once daily for 3 wk. For secondary prevention: 300 mg every 4 wk or 150 mg every 2 wk. Renal impairment: Dose adjustment may be needed. Reconstitution: Reconstitute: 600mg in 6 ml of water. Incompatibility: Reconstituted solutions must not be mixed with anything apart from water for inj, 5% glucose or 0.9% sodium chloride. Should not be mixed with other drugs or be administered with a bronchodilator in the same nebuliser.
Overdosage	Symptoms: cardiac rhythm disorders, including torsades de pointes. Treatment: symptomatic.
Special Precautions	History of asthma, smoking, hypokalaemia, hypomagnesaemia, coronary heart disease, bradycardia, history of ventricular arrhythmias, concomitant use with other drugs which prolong QT interval (if QTc interval >550 msec: consider alternative therapy), hypertension or hypotension, hyperglycaemia or hypoglycaemia, leucopenia, thrombocytopenia, anaemia, hepatic and renal impairment. Patients at risk of pneumothorax with nebulised therapy. Pregnancy and lactation. Patients should remain supine during admin due to risk of severe hypotension following admin. Monitor: BP, hepatic and renal function, blood-glucose and serum-calcium concentrations, blood counts and ECG. Direct IV inj should be avoided where possible and given slowly (at least 60-120 min); IM inj should be deep and administered in the buttocks.
Adverse Drug Reactions	Impaired renal function, acute renal failure, raised liver enzymes and haematological disturbances eg, leucopenia, anaemia, thrombocytopenia. Hypoglycaemia followed by hyperglycaemia and type 1 DM; acute pancreatitis. IM/IV: Sudden hypotension. IV (rapid injection): Dizziness, headache, vomiting, breathlessness, tachycardia and fainting. IM: Pain, swelling, rhabdomyolysis, sterile abscess formation and tissue necrosis at site of inj. Inhalation: Cough and bronchoconstriction; bitter taste. Hypocalcaemia, hyperkalaemia, skin rashes, fever, flushing, convulsions, hallucinations, GI effects e.g., nausea, vomiting, taste disturbances, abdominal pain and anorexia. Potentially Fatal: Cardiac arrhythmias, sudden hypotension; hypoglycaemia; pancreatitis; Stevens-Johnson syndrome, nephrotoxicity (in up to 25% of patients with pneumocystis pneumonia receiving parenteral treatment).
Drug Interactions	Increases risk of ventricular arrhythmias with amiodarone or levacetylmethadol. Increases risk of hypocalcaemia with foscarnet. Nephrotoxic drugs e.g. amphotericin B; increased risk of CNS depression and hypoglycaemic aggravation with alcohol; aminoglutethimide, carbamazepine, phenytoin, rifampicin may decrease levels of pentamidine; omeprazole, delavirdine, fluconazole, fluvoxamine, gemfibrozil, isoniazid, ticlopidine may increase levels of pentamidine. Potentially Fatal: Increased risk of QT interval prolongation with phenothiazines, TCAs, terfenadine, astemizole, IV erythromycin, halofantrine and quinolone antibiotics.
Storage	Intramuscular: Before reconstitution: protect from light and keep at room temperature (do not refrigerate as crystals may form); once reconstituted: store at 2-8 °C and use within 24 hr. Parenteral: Before reconstitution: protect from light and keep at room temperature (do not refrigerate as crystals may form); once reconstituted: store at 2-8 °C and use within 24 hr.
Mechanism of Action	Pentamidine isetionate inhibits oxidative phosphorylation and interferes with nucleotides and nucleic acid incorporation into the DNA/RNA, thus interfering with DNA/RNA, phospholipids and protein synthesis of susceptible protozoa. Absorption: IM: Absorbed well; inhalation: Limited systemic absorption. Distribution: IV: rapid (except to lung). Volume of distribution greater after IM administration. Excretion: Elimination half life: IV: 6 hr; IM: 9 hr (may be prolonged in renal impairment; excretion via urine (33-66% as unchanged drug). http://www.mims.com/Philippines/drug/info/pentamidine%20isetionate/?type=full&mtype=generic#Dosage