pentamidine

Absorption: Well absorbed parenterally; Minimal systemic absorption occurs following inhalation.

Distribution: Widely and extensively distributed but does not cross the blood-brain barrier. Concentrates in liver, kidneys, lungs, and spleen, with prolonged storage in some tissues.

Metabolism/Excretion: 1–30% excreted unchanged by the kidneys. Remainder of metabolic fate unknown.

Half-Life: 5–11 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	24 hr
Inhaln	unknown	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

History of previous anaphylactic reaction to pentamidine.

Use Cautiously in:

Hypotension;
Hypertension;
Hypoglycemia;
Hyperglycemia;
Hypocalcemia;
Leukopenia;
Thrombocytopenia;
Anemia;
Renal impairment (dose ↓ required);
Diabetes mellitus;
Liver impairment;
Cardiovascular disease;
Bone marrow depression, previous antineoplastic therapy, or radiation therapy;
Asthma (aerosol can induce bronchospasm);
OB: Safety not established during pregnancy; breast feeding not recommended.

Adv. Reactions/Side Effects ⬆ ⬇

For parenteral form, unless otherwise indicated

EENT:

inhalation

burning in throat

Neuro: anxiety, headache, confusion, dizziness, hallucinations

Resp:

inhalation

bronchospasm, cough

CV: ARRHYTHMIAS, hypotension, chest pain

GI: PANCREATITIS, abdominal pain, anorexia, drug-induced hepatitis, nausea, unpleasant metallic taste, vomiting

GU: nephrotoxicity

Derm: pallor, rash

Endo: hypoglycemia, hyperglycemia

F and E: hyperkalemia, hypocalcemia

Hemat: anemia, leukopenia, thrombocytopenia

Local:

phlebitis, pruritus, urticaria at IV site,

sterile abscesses at IM sites

Misc: ANAPHYLAXISALLERGIC REACTIONS INCLUDING , STEVENS-JOHNSON SYNDROME, chills, fever

Interactions ⬆ ⬇

Interactions listed for parenteral administration

Drug-drug:

Concurrent use with erythromycin IV may ↑ risk of potentially fatal arrhythmias.
Additive nephrotoxicity with other nephrotoxic agents, including aminoglycosides, amphotericin B, and vancomycin.
Additive bone marrow depression with antineoplastics or previous radiation therapy.
↑risk of nephrotoxicity, hypocalcemia, and hypomagnesemia with foscarnet.

Route/Dosage ⬆ ⬇

IV IM (Adults and Children >5 mo): 4 mg/kg once daily for 14–21 days (longer treatment may be required in AIDS patients; some patients may respond to 3 mg/kg/day).
Inhaln
(Adults ): NebuPent: 300 mg q 4 wk, using a Respirgard II jet nebulizer (150 mg q 2 wk has also been used).
Inhaln
(Children >5 yr): NebuPent: 300 mg q 4 wk, using a Respirgard II jet nebulizer (for patients who cannot tolerate trimethoprim/sulfamethoxazole; unlabeled).

Renal Impairment

IV (Adults ): CCr 10–30 mL/min- Administer normal dose q 24 hr; CCr <10 mL/min- Administer normal dose q 48 hr.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 300 mg/vial
Solution for aerosol use (NebuPent): 300 mg

Assessment ⬆ ⬇

Assess patient for infection (vital signs, sputum, WBC) and monitor respiratory status (rate, character, lung sounds, dyspnea, sputum) at beginning of and throughout therapy.
Obtain specimens for culture and sensitivity prior to initiating therapy. First dose may be given before receiving results.
Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome or toxic epidermal necrolysis. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
IV: IM: Monitor BP frequently during and following IM or IV administration of pentamidine. Patient should be lying down during administration. Sudden, severe hypotension may occur following a single dose. Resuscitation equipment should be immediately available.
Assess patient for signs of hypoglycemia (anxiety; chills; diaphoresis; cold, pale skin; headache; increased hunger; nausea; nervousness; shakiness) and hyperglycemia (drowsiness; flushed, dry skin; fruit-like breath odor; increased thirst; increased urination; loss of appetite), which may occur up to several mo after therapy is discontinued.
Pulse and ECG should be monitored prior to and periodically during therapy. Fatalities due to cardiac arrhythmias, tachycardia, and cardiotoxicity have been reported.
Assess patient for signs of pancreatitis (nausea, vomiting, abdominal pain, increased serum lipase, or amylase) periodically during therapy. May require discontinuation of therapy.
Inhaln: A tuberculin skin test, chest x-ray, and sputum culture should be performed prior to administration to rule out tuberculosis.

Lab Test Considerations:

IM, IV: Monitor blood glucose concentrations prior to, daily during, and for several mo following therapy. Severe hypoglycemia and permanent diabetes mellitus have occurred.
- Monitor BUN and serum creatinine prior to and daily during therapy to monitor for nephrotoxicity. Concentrations may be ↑.
- Monitor CBC and platelet count prior to and every 3 days during therapy. Pentamidine may cause leukopenia, anemia, and thrombocytopenia.
- May cause ↑ serum bilirubin, alkaline phosphatase, AST, and ALT concentrations. Monitor liver function tests prior to and every 3 days during therapy.
- Monitor serum calcium and magnesium concentrations prior to and every 3 days during therapy; may cause hypocalcemia and hypomagnesemia.
- May cause ↑ serum potassium concentrations.

Implementation ⬆ ⬇

Pentamidine must be given on a regular schedule for the full course of therapy. Administer missed doses as soon as remembered. If almost time for the next dose, skip the missed dose and return to the regular schedule. Do not double doses.
IM: Dilute 300 mg of pentamidine with 3 mL of sterile water for injection for a concentration of 100 mg/mL. IM administration should be used only for patients with adequate muscle mass and given deep IM via Z-track technique. May cause sterile abscesses.
Inhaln: If using inhalation bronchodilator, administer bronchodilator 5–10 min prior to pentamidine administration.
- Administer in a well-ventilated area.
- Administration with patient in supine or recumbent position appears to provide a more uniform distribution of pentamidine.
- NebuPent Dilute 300 or 600 mg (for prophylaxis or treatment, respectively) in 6 mL of sterile water for injection. Place reconstituted solution into Respirgard II nebulizer. Do not dilute with 0.9% NaCl or admix with other medications, as solution will form a precipitate. Do not use Respirgard II nebulizer for other medications.
- Administer inhalation dose through nebulizer until chamber is empty, approximately 30–45 min.
- Administer with the flow rate of the nebulizer at the midflow mark (5–7 L/min) over approximately 15 min until the chamber is empty.

IV Administration:

Intermittent Infusion: Diluent: To reconstitute, add 3–5 mL of sterile water for injection or D5W to each 300-mg vial for a concentration of 100, 75, or 60 mg/mL, respectively. Withdraw dose and dilute further in 50–250 mL of D5W. Solution is stable for 48 hr at room temperature. Discard unused portions.Concentration: Not to exceed 6 mg/mL for administration.
Rate: Administer slowly over 1–2 hr.

Patient/Family Teaching ⬆ ⬇

Inform patient of the importance of completing the full course of pentamidine therapy, even if feeling better.
IV: Instruct patient to notify health care professional promptly if signs and symptoms of pancreatitis, rash, fever; sore throat; signs of infection; bleeding of gums; unusual bruising; petechiae; or blood in stool, urine, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should not be given IM injections or rectal thermometers. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, as these may precipitate gastric bleeding.
- Caution patient to make position changes slowly to minimize orthostatic hypotension.
Inhaln: Advise patient that an unpleasant metallic taste may occur with pentamidine administration but is not significant.
- Inform patients who continue to smoke that bronchospasm and coughing during therapy are more likely.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇