AmBisome Side Effects

Please note - some side effects for AmBisome may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of AmBisome - for the Consumer

AmBisome

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using AmBisome:

Chills; coughing; fever; headache; loss of appetite; muscle or joint pain; nausea; rapid heartbeat; sleeplessness; stomach pain; weight loss.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; chest pain; convulsions; dark, bloody stools; decreased urination; diarrhea; dizziness; easy bruising or bleeding; fast breathing; fast or irregular heartbeat; hearing loss; pain, redness, or inflammation at the injection site; swelling of the hands or feet; unusual tiredness or weakness; vomiting; yellowing of eyes or skin.

AmBisome Side Effects - for the Professional

AmBisome

The following adverse events are based on the experience of 592 adult patients (295 treated with AmBisome and 297 treated with amphotericin B deoxycholate) and 95 pediatric patients (48 treated with AmBisome and 47 treated with amphotericin B deoxycholate) in Study 94-0-002, a randomized double-blind, multi-center study in febrile, neutropenic patients. AmBisome and amphotericin B were infused over two hours.

The incidence of common adverse events (incidence of 10% or greater) occurring with AmBisome compared to amphotericin B deoxycholate, regardless of relationship to study drug, is shown in the following table:

AmBisome was well tolerated. AmBisome had a lower incidence of chills, hypertension, hypotension, tachycardia, hypoxia, hypokalemia, and various events related to decreased kidney function as compared to amphotericin B deoxycholate.

In pediatric patients (16 years of age or less) in this double-blind study, AmBisome compared to amphotericin B deoxycholate had a lower incidence of hypokalemia (37% versus 55%), chills (29% versus 68%), vomiting (27% versus 55%), and hypertension (10% versus 21%). Similar trends, although with a somewhat lower incidence, were observed in open-label, randomized Study 104-14 involving 205 febrile neutropenic pediatric patients (141 treated with AmBisome and 64 treated with amphotericin B deoxycholate). Pediatric patients appear to have more tolerance than older individuals for the nephrotoxic effects of amphotericin B deoxycholate.

The following adverse events are based on the experience of 244 patients (202 adult and 42 pediatric patients) of whom 85 patients were treated with AmBisome 3 mg/kg, 81 patients were treated with AmBisome 5 mg/kg and 78 patients treated with amphotericin B lipid complex 5 mg/kg in Study 97-0-034, a randomized double-blind, multi-center study in febrile, neutropenic patients. AmBisome and amphotericin B lipid complex were infused over two hours. The incidence of adverse events occurring in more than 10% of subjects in one or more arms regardless of relationship to study drug are summarized in the following table:

The following adverse events are based on the experience of 267 patients (266 adult patients and 1 pediatric patient) of whom 86 patients were treated with AmBisome 3 mg/kg, 94 patients were treated with AmBisome 6 mg/kg and 87 patients treated with amphotericin B deoxycholate 0.7 mg/kg in Study 94-0-013 a randomized, double-blind, comparative multi-center trial, in the treatment of cryptococcal meningitis in HIV positive patients. The incidence of adverse events occurring in more than 10% of subjects in one or more arms regardless of relationship to study drug are summarized in the following table:

Infusion Related Reactions

In Study 94-0-002, the large, double-blind study of pediatric and adult febrile neutropenic patients, no premedication to prevent infusion related reaction was administered prior to the first dose of study drug (Day 1). AmBisome-treated patients had a lower incidence of infusion related fever (17% versus 44%), chills/rigors (18% versus 54%) and vomiting (6% versus 8%) on Day 1 as compared to amphotericin B deoxycholate-treated patients.

The incidence of infusion related reactions on Day 1 in pediatric and adult patients is summarized in the following table:

Cardiorespiratory events, except for vasodilatation (flushing), during all study drug infusions were more frequent in amphotericin B-treated patients as summarized in the following table:

The percentage of patients who received drugs either for the treatment or prevention of infusion related reactions (e.g., acetaminophen, diphenhydramine, meperidine and hydrocortisone) was lower in AmBisome-treated patients compared with amphotericin B deoxycholate-treated patients.

In the empirical therapy study 97-0-034, on Day 1, where no premedication was administered, the overall incidence of infusion related events of chills/rigors was significantly lower for patients administered AmBisome compared with amphotericin B lipid complex. Fever, chills/rigors and hypoxia were significantly lower for each AmBisome group compared with the amphotericin B lipid complex group. The infusion related event hypoxia was reported for 11.5% of amphotericin B lipid complex-treated patients compared with 0% of patients administered 3 mg/kg per day AmBisome and 1.2% of patients treated with 5 mg/kg per day AmBisome.

Day 1 body temperature increased above the temperature taken within 1 hour prior to infusion (preinfusion temperature) or above the lowest infusion value (no preinfusion temperature recorded).

Patients were not administered premedications to prevent infusion related reactions prior to the Day 1 study drug infusion.

In Study 94-0-013, a randomized double-blind multicenter trial comparing AmBisome and amphotericin B deoxycholate as initial therapy for cryptococcal meningitis, premedications to prevent infusion related reactions were permitted. AmBisome treated patients had a lower incidence of fever, chill/rigors and respiratory adverse events as summarized in the following table:

There have been a few reports of flushing, back pain with or without chest tightness, and chest pain associated with AmBisome administration; on occasion this has been severe. Where these symptoms were noted, the reaction developed within a few minutes after the start of infusion and disappeared rapidly when the infusion was stopped. The symptoms do not occur with every dose and usually do not recur on subsequent administrations when the infusion rate is slowed.

Toxicity and Discontinuation of Dosing

In Study 94-0-002, a significantly lower incidence of grade 3 or 4 toxicity was observed in the AmBisome group compared with the amphotericin B group. In addition, nearly three times as many patients administered amphotericin B required a reduction in dose due to toxicity or discontinuation of study drug due to an infusion related reaction compared with those administered AmBisome.

In empirical therapy study 97-0-034, a greater proportion of patients in the amphotericin B lipid complex group discontinued the study drug due to an adverse event than in the AmBisome groups.

Less Common Adverse Events

The following adverse events also have been reported in 2% to 10% of AmBisome-treated patients receiving chemotherapy or bone marrow transplantation, or had HIV disease in six comparative, clinical trials:

Body as a Whole

Abdomen enlarged, allergic reaction, cellulitis, cell mediated immunological reaction, face edema, graft versus host disease, malaise, neck pain, and procedural complication.

Cardiovascular System

Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, cardiomegaly, hemorrhage, postural hypotension, valvular heart disease, vascular disorder, and vasodilatation (flushing).

Digestive System

Anorexia, constipation, dry mouth/nose, dyspepsia, dysphagia, eructation, fecal incontinence, flatulence, hemorrhoids, gum/oral hemorrhage, hematemesis, hepatocellular damage, hepatomegaly, liver function test abnormal, ileus, mucositis, rectal disorder, stomatitis, ulcerative stomatitis, and veno-occlusive liver disease.

Hemic & Lymphatic System

Anemia, coagulation disorder, ecchymosis, fluid overload, petechia, prothrombin decreased, prothrombin increased, and thrombocytopenia.

Metabolic & Nutritional Disorders

Acidosis, amylase increased, hyperchloremia, hyperkalemia, hypermagnesemia, hyperphosphatemia, hyponatremia, hypophosphatemia, hypoproteinemia, lactate dehydrogenase increased, nonprotein nitrogen (NPN) increased, and respiratory alkalosis.

Musculoskeletal System

Arthralgia, bone pain, dystonia, myalgia, and rigors.

Nervous System

Agitation, coma, convulsion, cough, depression, dysesthesia, dizziness, hallucinations, nervousness, paresthesia, somnolence, thinking abnormality, and tremor.

Respiratory System

Asthma, atelectasis, hemoptysis, hiccup, hyperventilation, influenza-like symptoms, lung edema, pharyngitis, pneumonia, respiratory insufficiency, respiratory failure, and sinusitis.

Skin & Appendages

Alopecia, dry skin, herpes simplex, injection site inflammation, maculopapular rash, purpura, skin discoloration, skin disorder, skin ulcer, urticaria, and vesiculobullous rash.

Special Senses

Conjunctivitis, dry eyes, and eye hemorrhage.

Urogenital System

Abnormal renal function, acute kidney failure, acute renal failure, dysuria, kidney failure, toxic nephropathy, urinary incontinence, and vaginal hemorrhage.

The following infrequent adverse experiences have been reported in post-marketing surveillance, in addition to those mentioned above: angioedema, erythema, urticaria, bronchospasm, cyanosis/hypoventilation, pulmonary edema, agranulocytosis, hemorrhagic cystitis.

Clinical Laboratory Values

The effect of AmBisome on renal and hepatic function and on serum electrolytes was assessed from laboratory values measured repeatedly in Study 94-0-002. The frequency and magnitude of hepatic test abnormalities were similar in the AmBisome and amphotericin B groups. Nephrotoxicity was defined as creatinine values increasing 100% or more over pretreatment levels in pediatric patients, and creatinine values increasing 100% or more over pretreatment levels in adult patients provided the peak creatinine concentration was >1.2 mg/dL. Hypokalemia was defined as potassium levels ≤2.5 mmol/L any time during treatment.

Incidence of nephrotoxicity, mean peak serum creatinine concentration, mean change from baseline in serum creatinine, and, incidence of hypokalemia in the double-blind randomized study were lower in the AmBisome group as summarized in the following table:

The effect of AmBisome (3 mg/kg/day) vs. amphotericin B (0.6 mg/kg/day) on renal function in adult patients enrolled in this study is illustrated in the following figure:

In empirical therapy study 97-0-034, the incidence of nephrotoxicity as measured by increases of serum creatinine from baseline was significantly lower for patients administered AmBisome (individual dose groups and combined) compared with amphotericin B lipid complex.

Incidence of Nephrotoxicity

The following graph shows the average serum creatinine concentrations in the compassionate use study and shows that there is a drop from pretreatment concentrations for all patients, especially those with elevated (greater than 1.7 mg/dL) pretreatment creatinine concentrations.

The incidence of nephrotoxicity in Study 94-0-013, comparative trial in cryptococcal meningitis was lower in the AmBisome groups as shown in the following table:

Side Effects by Body System

General

General reactions during amphotericin B liposomal infusions, such as fever and chills/rigors, have been reported. These symptoms usually began within a few minutes of initiation of an amphotericin B liposomal infusion. Slowing the rate of infusion has lessened or controlled symptoms. Severe infusion-related side effects associated with conventional amphotericin B administration have been lessened by pretreatment/treatment with corticosteroids, acetaminophen, antihistamines, and meperidine.

Metabolic

Metabolic side effects have included hypokalemia (4.2% to 51.1%), hypomagnesemia (15.3% to 48.9%), hyperglycemia (8.2% to 23%), hypocalcemia (4.9% to 18.4%), hypervolemia (8.2% to 12.2%), and hyponatremia (2% to 11.6%), hypernatremia (4.1%). Acidosis, increased amylase, hyperchloremia, hyperkalemia, hypermagnesemia, hyperphosphatemia, hypophosphatemia, hypoproteinemia, increased lactate dehydrogenase, increased nonprotein nitrogen, and respiratory alkalosis have been reported in 2% to 10% of patients.

Metabolic changes have occurred less frequently with amphotericin B liposomal than with conventional amphotericin B.

Four patients with invasive fungal infections experienced severe hyperphosphatemia coincident with amphotericin B liposomal therapy. Resolution of the side effect occurred after transition to amphotericin B lipid complex. Hyperphosphatemia may be reported more commonly in patients with mild to moderate renal insufficiency.

Renal

Renal toxicity has been reported less frequently with amphotericin B liposomal than with conventional amphotericin B.

Renal side effects have included increased serum creatinine (5.5% to 47%), BUN (7.4% to 22%), and nephrotoxicity (18.7%). Abnormal renal function (including oliguria and anuria), acute kidney failure, acute renal failure, kidney failure, and toxic nephropathy have been reported in 2% to 10% of patients. Decreased serum concentrations of potassium, magnesium, sodium, and calcium have often accompanied amphotericin-induced nephrotoxicity.

Hematologic

Hematologic side effects have included anemia (2% to 47.9%), leukopenia (15.1% to 17%), and thrombocytopenia (2% to 12.8%). Coagulation defects/disorder, ecchymosis, fluid overload, petechiae, decreased prothrombin, and increased prothrombin have been reported in 2% to 10% of patients. Agranulocytosis has been reported during postmarketing experience.

Cardiovascular

Cardiovascular side effects have included hypertension (7.9 to 19.8%), tachycardia (9.4% to 18.5%), hypotension (7.4% to 14.3%), chest pain (8.2% to 12%), and phlebitis (9.3% to 10.6%). Infusion-related effects have included tachycardia (2.3% to 9.9%), hypertension (2.3% to 8.6%), vasodilatation (5.2%), and hypotension (3.5%). Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, cardiomegaly, hemorrhage, postural hypotension, valvular heart disease, and vasodilatation (flushing) have been reported in 2% to 10% of patients. Cardiac failure and cardiomyopathy have also been reported.

Respiratory

Respiratory side effects have included dyspnea (17.6% to 23%), increased cough (2.1% to 17.8%), lung disorder (13.6% to 17.8%), epistaxis (8.6% to 14.9%), pleural effusion (12.5%), rhinitis (11.1%), and hypoxia (6.2% to 7.6%). Infusion-related reactions have included dyspnea (4.7% to 9.9%), hyperventilation (1.2%), and hypoxia (0.3% to 1.2%). Asthma, atelectasis, hemoptysis, hiccup, hyperventilation, influenza-like symptoms, lung edema, pharyngitis, pneumonia, respiratory insufficiency, respiratory failure, and sinusitis have been reported in 2% to 10% of patients. Bronchospasm, cyanosis/hypoventilation, and pulmonary edema have been reported during postmarketing experience.

Gastrointestinal

Gastrointestinal side effects have included nausea (16.3% to 39.7%), vomiting (10.5% to 31.8%), diarrhea (10.5% to 30.3%), constipation (2% to 15.1%), anorexia (2% to 14%), and gastrointestinal hemorrhage (9.9%). Infusion-related reactions have included vomiting (5.9% to 16%) and nausea (8.6% to 14%). Dry mouth/nose, dyspepsia, dysphagia, eructation, fecal incontinence, flatulence, hemorrhoids, gum/oral hemorrhage, hematemesis, ileus, mucositis, rectal disorder, stomatitis, and ulcerative stomatitis have been reported in 2% to 10% of patients. Epigastric pain and cramping have been reported less frequently.

Other

Other side effects have included chills/rigors (40% to 48.1%), chills (47.5%), abdominal pain (7% to 19.8%), blood product transfusion reaction (8.6% to 18.4%), peripheral edema (14.6%), edema (12.3% to 14.3%), pain (14%), sepsis (7.4% to 14%), asthenia (6.2% to 13.1%), infection (11.1% to 12.8%), back pain (12%), and procedural complication (2% to 9.6%). Infusion-related reactions have included chills/rigors (6% to 23.5%) and fever (up to 19.8%). A few cases of flushing, back pain (with or without chest tightness), and chest pain have been reported with amphotericin B liposomal administration, and occasionally this has been severe. Enlarged abdomen, face edema, malaise, and neck pain have been reported in 2% to 10% of patients.

Nervous system

Nervous system side effects have included headache (9.4% to 19.8%), insomnia (17% to 22.1%), confusion (8.6% to 12.9%), dizziness (2% to 8.5%), and peripheral neuropathy. Agitation, coma, convulsion, cough, dysesthesias, paresthesia, tremor, and somnolence have been reported in 2% to 10% of patients.

Hepatic

Hepatic side effects have included elevated alkaline phosphatase (7.1% to 22.2%), bilirubin (5.2% to 18.1%), alanine transaminase (ALT, 8.9% to 14.6%), aspartate transaminase (AST, 7.6% to 12.8%), and abnormal liver function tests (2% to 12.8%). Hepatocellular damage, hepatomegaly, and veno-occlusive liver disease have been reported in 2% to 10% of patients.

Dermatologic

Dermatologic side effects have included rash (4.7% to 24.8%), pruritus (10.8%), sweating (7%), flushing (4.2%). Alopecia, cellulitis, dry skin, herpes simplex, maculopapular rash, purpura, skin discoloration, skin disorder, skin ulcer, urticaria, and vesiculobullous rash have been reported in 2% to 10% of patients. Erythema has been reported during postmarketing experience.

Genitourinary

Genitourinary side effects have included hematuria (14%). Dysuria, urinary incontinence, and vaginal hemorrhage have been reported in 2% to 10% of patients. Hemorrhagic cystitis has been reported during postmarketing experience.

Psychiatric

Psychiatric side effects have included anxiety (7.4% to 13.7%). Depression, hallucinations, nervousness, and abnormal thought processes have been reported in 2% to 10% of patients.

Musculoskeletal

Musculoskeletal side effects have included arthralgia, bone pain, dystonia, myalgia, and rigors in 2% to 10% of patients.

Hypersensitivity

Hypersensitivity side effects have included allergic reaction (2% to 10%). Hypersensitivity reactions have presented as bronchospasm, wheezing, or anaphylactoid reactions. Angioedema and urticaria have been reported during postmarketing experience.

Local

Local side effects have included inflammation at the injection site in 2% to 10% of patients.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.