Interacting drugs- summary

+ Amphotericin B

Antineoplastic agents

concurrent administration enhance the potential for renal toxicity, bronchospasm anfd hypertension

Corticosteroids

concurrent administration potentiate hypokalemia and predispose the patient to cardiac dysfunction. Do not give unless necessary to control adverse reactions

Zidovudine

concurrent administratin increases neurotoxicity and nephrotoxicity. If used concomittantly, closely monitor renal and hematologic function

Amphotericin B +

Nephrotoxic agents

incr nephrotoxic effects of cyclosporine increased. Take extra care when administering amphotericin B with other nephrotoxic agents

Digitalis glycosides

concurent administration induce hypokalemia and potentiate digitalis toxicity

Flucytosine

flucytosine toxicity increased by increasing its cellular uptake or impair or impair renal excretion

Neuromuscular blocking

ampotericin B-induced hypokalemia may enhance the curariform affect agents (NNBs) of skeletal muscle relaxants

Prevention of adverse reactions

Most patients will exhibit some intolerance, often at less than full therapeutic dosage.

Severe reactions may be lessened by giving aspirin, antipyretics(eg acetaminiophen) antihistamines and antiemetics before the infusion and by maintaining sodium balance.

Administration on alternate days may decrease anorexia and phlebits.

Small doses of IV adrenal corticosteroids given prior to or during infusion may decrease febrile conditions.

Keep the dosage and duration of such corticosteroid therapy to a minimum.

Most frequent -

General toxic reactions- fever ( sometimes with shaking chills), headache, anorexia, malaise, generalised pain, including muscle and joint pains

Respiratory- respiratory failure, respiratorty disorder, pneumonia Metabolic/ Nutrional- bilirubinemia, increased serum creatinine, acidosis

Renal- hyperkalemia, azotemia, kidney failure, renal tubular acidosis.

GI- nausea, vomiting, dyspepsia, diarrhea, cramping, epigastric pain, abdominal pain. Hematologic- normochromic, normocytic anemia.

Local- venous pain at the injection site with phlebitis, an thrombophlebitis Miscellaneous- weight loss, multiple organ failure, sepsis, infection, rash

Less frequent

Hypersensitivity- broncospasm, wheezing, asthma

Cardiovascular- arrhythmias, ventricular fibrillation,cardiac arrest, hypertension, hypotension, cardiac faliure, pulmonary edema, shock, myocardial infarction, tachypnea, pulmonary embolus, cardiomyopathy

Hemotologic- caogulation defects, thrmbocytopenia, leukopenia, agranulcytosis, eosionophillia, leukocytosis

CNS- peripheral neuropathy, convulsions, encephalopathy, extrapyrimidal symptoms, other neurological symptoms.

Special senses- hearing loss, tinnitus, transcient vertigo, blurred vision, diplopia

GI- hemorrhagic gastroenteritis, acute liver failure, hepatitis, jaundice, anorexia,

Renal- acute renal failure, decreased renal function, anuria, oliguria, permanent damage is often related to large total dose (>5g)

Dermatologic- maculopapular rash, pruritus,(without rash), exfoliative dermatitis, erythema multiforme.

Miscellaneous- anaphylactoid reactions, flushing, dyspnea, impotence, myasthenia

Benefits of use must be weighed against drugs untoward and dangerous side effects.Hypersens.

Special precautions:

Renal impairment.

Monitoring-

Perform BUN and serum creatinine or endogenous creatinine clearance tests at least weekly during therapy.

Discontinue therapy if liver function test results are abnormal (elevated alkaline phosphatase and bilirubin)

Monitor renal function frequently during amphotericin B therapy.

It is also advisable to monitor liver function, serum electrlytes (particularly magnesium and potassium), blood counts and hemoglobin concentrations on a regular basis.

Prolonged therapy- is usually necessary. Use only in hospitalized patients or in those under close medical observation.

Therapy interruption- whenever medication is interrupted for > 7 days, resume therapy with the lowest dosage level. Increase gradually.

Pulmonary reactions- characterized by acute dyspnea, hypoxemia, and interstitial infiltrates have been observed in neutropenic patients receiving amphotericin B and leucocyte transfusions.

Administer amphotericin B cautiously in patients receiving leucocyte transfusions and separate the infusion as far as possible from the time of leuckocyte transfusion

Laboratory tests- Serum electrolyte abnormalities- hypomagnesemia, hypocalcemia.

Renal function abnormalities- increased BUN

Other test abnormalities- acidosis, hypermylasemia, hypoglycemia, hyperglycemia.

Warnings

Nephrotoxicity- renal damage the most important toxic effect is a limiting factor for the use of amphotericin B. Renal dysfunction usually improves upon interrruption of therapy, dose reduction or increased dosing interval, however some permanent impairment often occurs.

Acute reactions - including fever, shaking chills, hypotension, anorexia, vomiting, nausea, headache and tachypnea are common 1 to 3 hours after starting an IV infusion. These reactions are usually severe with first few doses of amphotericin B and usually diminish with susequent doses.

Rapid infusion- has been associated with hypotension, hypokalemia, and arrhythmias and shock and should be avoided. Diabetic control must be instituted before successful treatment with amphotericin B can be accomplished.

Hypersensitivity- If severe respiratory distress occurs, discontinue the infusion immediately. Do not give further infusions.

Renal function impairment- use with care in patients with reduced renal function, frequent monitoring is recommended.

Pregnancy- Use during pregnancy only if clearly needed.

Lactation- it is not known whether amphotericin B is excreted in breast milk. However, consider discontinuing nursing or eliminating IV amphotericn B.

Children- safety and efficacy in children have not been established.

Indications:

Monilasis, Coccidomycosis, Histoplasmosis.

Dosage:

Infuse test dose 1mg to determine patient tolerance. Starting daily dose is 0.25mg/kg.Total daily dose may range upto 1mg/kg. Do not exceed a total daily dose of 1.5mg/kg.

Overdosage- Symptoms Cardio-respiratory arrest

Treatment.

1. Discontinue therapy, monitor clinical status

2. Administer supportive therapy

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Hypokalemia-

The principal causes of potassium depletion or hypokalemia are-

1. Gastrointestinal - dificient dietary intake

2. Gastrointestinal lossess due to voniting, diarrhrea

3. Renal - diuretics

4. Excessive mineralocorticoid effects

5. Renal tubular diseases

Myopathy or Myalgia-

Drugs causing adverse reactions-

1. Corticosteroids

2. Chloroquine

3. Clofibrate

4. Oral contraceptives

5. Amphotericin B

6. Carbenoxolone

Drugs causing adverse reactions-

1. Diuretics

2. Laxative abuse

3. Corticosteroids

4. Ampotericin B

5. Alkai induced alkalosis

6. Insulin

7. Osmotic diuretics

8. Carbenoxolone

9. Gentamicin

10. Degraded tetracycline

11. Vitamin B12

Amphotericin B

1. Individual allergy - Tell your doctor, if you have ever had any unusual or allergic reaction to amphotericin B . Also tell your doctor if you are allergic to any other substance, food, or preservatives.

2. Pregnancy - Amphoericin B has not been reported to cause birth defects or other problems in humans.

3. Breast feeding - Amphoterin B has not ben reported to cause problems in nursing babies

4. Children - Although there is no specific information comparing use of Amphotericin B in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

5. Other medicines - Certain medicines should not be used together due to interactions. However, tell your doctor if you are using any other prescription drugs eg., cancer medicines, antithyroid agents, azathioprine, chloramphenicol, colchicine, cyclophosphamide, antiviral agents, corticosteroids, digitalis glycosides. methotrexate, penicillamine

6. Other medical problems - Tell your doctor, if you have any other medical problems eg. liver disease.

7. Dose - Take this medicine as directed by your physician. Do not miss any doses. 8.. Storage - Keep out of reach of children. Do not store in the bath room, near the kitchen sink or in damp places. Heat or moisture may cause the medicine to break down.

Pharmacology:

Amphotericin B is fungistatic or fungicidal. It acts by binding to sterols in the fungal cell membrane with a resultant change in membrane permeability, allowing leakage of a variety of small molecules.

Pharmacokinetics:

Penetration of the drug into inflamed pleural cavities and joints is good. The drug is slowly excreted by the kidneys with 2% to 5% as the biologically active form

Reports not available.

Pregnancy:

Adequate and well controlled studies have not been conducted, therfore use during pregnancy only if needed

Lactation:

Not known whether Amphotericin is excreted in breast milk. Consider discontinuing nursing or eliminating Amphotericin use.

Children: Safety and efficacy in children have not been established.