For the Consumer

Applies to daptomycin: intravenous powder for solution

Along with its needed effects, daptomycin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking daptomycin:

More common

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• fever
• rapid weight gain
• tingling of the hands or feet
• unusual weight gain or loss

Less common

• Agitation
• black, tarry stools
• bladder pain
• bloody or cloudy urine
• blurred vision
• chest pain or discomfort
• chills
• confusion
• cough
• decreased awareness or responsiveness
• decreased frequency or amount of urine
• depression
• diarrhea
• difficult or labored breathing
• difficult, burning, or painful urination
• dilated neck veins
• dizziness
• dry mouth
• dryness and peeling of the skin
• extreme fatigue
• fainting
• faintness or lightheadedness when getting up suddenly from a lying or sitting position
• fast heartbeat
• frequent urge to urinate
• headache
• hostility
• increased blood pressure
• increased thirst
• irregular breathing
• irregular heartbeat
• irritability
• itching in the genital or other skin areas
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• lightheadedness
• loss of appetite
• loss of consciousness
• lower back or side pain
• mood changes
• muscle pain or cramps
• muscle twitching
• nausea
• nervousness
• numbness or tingling in the hands, feet, or lips
• pale skin
• pounding in the ears
• rapid weight gain
• rapid, shallow breathing
• seizures
• severe sleepiness
• slow or fast heartbeat
• sneezing
• sore throat
• stomach pain
• sweating
• swelling of the face, fingers, ankles, or hands
• tightness in the chest
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• vomiting of blood or material that looks like coffee grounds
• weight gain

Rare

• Bleeding gums
• blood in the urine or stools
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• clay-colored stools
• dark urine
• difficulty with moving
• drowsiness
• eye pain
• feeling of warmth
• feeling unusually cold
• general feeling of illness
• hives, itching, or rash
• hoarseness
• increase in bone pain
• irritation
• joint pain, stiffness, or swelling
• loss of appetite
• mood or mental changes
• muscle aching or cramping
• muscle spasms (tetany) or twitching
• no blood pressure or pulse
• pinpoint red spots on the skin
• rapid or irregular heartbeat
• redness of the face, neck, arms, and occasionally, upper chest
• redness, blistering, peeling, or loosening of the skin
• shivering
• skin rash, encrusted, scaly, and oozing
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• stopping of the heart
• swelling of the eyelids, face, lips, hands, or feet
• swollen glands or joints
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• trembling
• troubled breathing or swallowing
• twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• unpleasant breath odor
• unusual bleeding or bruising
• vomiting of blood
• yellow eyes or skin

Incidence not known

• Diarrhea, watery, and severe, which may also be bloody
• dry cough
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• stomach cramps or tenderness
• unusual weight loss

Some side effects of daptomycin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• difficulty having a bowel movement

Less common

• Anxiety
• back pain
• blurred vision
• cold sweats
• cool, pale skin
• decreased appetite
• depression
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• increased urination
• itching of the vagina or outside genitals
• lack or loss of strength
• limb pain
• nervousness
• nightmares
• pain during sexual intercourse
• shakiness
• slurred speech
• sweating
• thick, white, curd-like vaginal discharge without odor or with mild odor
• trouble sleeping
• unexplained weight loss

Rare

• Bad, unusual, or unpleasant (after) taste
• belching
• change in taste
• continuing ringing or buzzing or other unexplained noise in the ears
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• feeling of fullness
• hearing loss
• heartburn
• indigestion
• pain or discomfort in the chest, upper stomach, or throat
• passing gas
• pressure in the stomach
• red, sore eyes
• seeing, hearing, or feeling things that are not there
• sensation of spinning
• sore mouth or tongue
• swelling of the abdominal or stomach area
• swelling or inflammation of the mouth
• white patches in the mouth or on the tongue

For Healthcare Professionals

Applies to daptomycin: intravenous powder for injection

General

In phase 3 complicated skin and skin structure infection trials, this drug was discontinued in 2.8% of patients due to a side effect, while comparator was discontinued in 3% of patients. In the Staphylococcus aureus bacteremia/endocarditis trial, this drug was discontinued in 16.7% of patients due to a side effect, while comparator was discontinued in 18.1% of patients.

In phase 3 community-acquired pneumonia trials, the death rate and rates of serious cardiorespiratory side effects were higher with this drug than comparator due to lack of therapeutic efficacy.

Musculoskeletal

Common (1% to 10%): Elevated creatine phosphokinase (CPK), limb pain

Uncommon (0.1% to 1%): Myalgia, muscle cramps, myositis, increased myoglobin, muscle weakness, muscle pain, arthralgia, muscle pain/weakness symptoms associated with CPK elevations to greater than 4 times the upper limit of normal (4 x ULN)

Frequency not reported: Pain in extremity, back pain, osteomyelitis, muscle twitching, myopathy (with minor increases in CPK), rhabdomyolysis (with secondary acute renal failure), severe myopathy (with possible hepatotoxicity)

Postmarketing reports: Rhabdomyolysis (some cases involved coadministration with HMG-CoA reductase inhibitors)

In clinical studies, 0.2% of patients had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4 x ULN. After discontinuation of this drug, CPK returned to normal within 7 to 10 days and symptoms resolved within 3 days.

A 45-year-old female with refractory acute myeloid leukemia was admitted to the blood and marrow transplant unit for a second attempt to induce remission with myeloablative chemotherapy of high-dose cytarabine. Two months prior, the patient's first course of induction therapy was complicated by neutropenic fever and vancomycin- resistant Enterococcus faecium (VRE) bacteremia that was treated with linezolid for 14 days. The patient was also receiving aztreonam, levofloxacin, acyclovir, amphotericin B lipid complex, and azithromycin. Once her clinical status stabilized, she was transferred from the intensive care unit (ICU) back to the blood and marrow transplant unit. After receiving 8 of 12 scheduled doses of cytarabine, the patient required readmission to the medical ICU due to a decrease in mental status, supraventricular tachycardia, and hypotension. Cultures of blood and urine samples at the time of her transfer showed VRE with intermediate resistance to linezolid. The patient, who was neutropenic at this time, was started on IV daptomycin 550 mg (6 mg/kg) every 24 hours. The patient's baseline CPK was 108 units/L and serum creatinine level was 0.8 mg/dL. Over the following 7 days, the patient's CPK level gradually increased, and on day 10 of daptomycin therapy, her CPK level was 996 units/L, BUN was 73 mg/dL, and serum creatinine level was 1.9 mg/dL. To evaluate for rhabdomyolysis, urine myoglobin was measured and reported at 30,890 ng/mL. Rhabdomyolysis was diagnosed based on increased CPK and urine myoglobin level in a patient with acute renal failure. Daptomycin was discontinued and the patient was started on treatment for rhabdomyolysis. Despite aggressive hydration and diuresis, CPK and urine myoglobin levels continued to increase up to 5350 units/L and 47,166 ng/mL, respectively. Over 2 weeks, the patient's CPK and urine myoglobin levels slowly resolved. The final CPK and urine myoglobin levels measured were 3395 units/L and 451 ng/mL, respectively.

In another case, a 53-year-old African-American female with a history of hypertension, diabetes mellitus, and peripheral vascular disease was admitted to the hospital and an MRI revealed L5-S1 discitis and osteomyelitis. After an 8-week course of empirical antibiotic therapy with vancomycin and levofloxacin, an open biopsy was performed. Specimens from the biopsy cultured positive for Torulopsis glabrata, VRE, and methicillin-resistant S aureus (MRSA) and the patient was started on daptomycin 360 mg (6 mg/kg) IV as a single daily dose and voriconazole 250 mg twice daily. Ten days after starting this drug, the patient developed generalized muscular weakness that progressed to the point she was unable to get out of bed. The patient then developed nonoliguric acute renal failure with a serum creatinine of 27 mg/mL up from baseline of 9 mg/mL. A CPK level drawn was elevated to 21,243 units/L and was associated with elevated levels: AST 375 units/L, ALT 219 units/L, and LDH 666 units/L. Urinalysis was positive for hemoglobin, myoglobin, and RBCs which conferred a diagnosis of acute renal failure secondary to drug-induced rhabdomyolysis. After this drug was discontinued and IV fluid was administered to alkalinize the urine, renal function, CPK, and liver function tests returned to baseline as well as dissipation of muscular weakness. Myoglobin, hemoglobin, and RBCs disappeared from urine as well.

In another similar case, a 52-year-old male with a history hepatitis C, IV drug abuse, idiopathic thrombocytopenia, and hyperlipidemia was admitted to the hospital and an MRI revealed findings compatible with L3-L4 discitis and osteomyelitis. He was started on vancomycin but it was discontinued after a rash developed. Daptomycin was started at 500 mg (6.5 mg/kg) IV as a single daily dose. The patient was also on simvastatin; however, it was discontinued prior to starting this drug. After 9 days of therapy, the patient developed generalized muscle weakness progressing to the point where he was unable to get out of bed. The patient's CPK rose to 20,771 units/L from a baseline of 102 units/L. AST 239 units/L and ALT 40 units/L were elevated from baseline and alkaline phosphatase was elevated to 118 units/L. This drug was discontinued and the patient was admitted to the ICU for close monitoring and hydration. The patient slowly improved and recovered all muscle strength and within 2 weeks his enzymes returned to baseline.

Increased myoglobin has also been reported during postmarketing experience.

Psychiatric

Common (1% to 10%): Insomnia, anxiety

Uncommon (0.1% to 1%): Mental status change

Frequency not reported: Hallucination, confusion

Other

Common (1% to 10%): Pyrexia, asthenia, serious gram-negative infections (including bloodstream infections, cholangitis, alcoholic pancreatitis, sternal osteomyelitis/mediastinitis, bowel infarction, recurrent Crohn's disease, recurrent line sepsis, recurrent urosepsis), chest pain, edema, sepsis, bacteremia, fungal infections, candidal infection

Uncommon (0.1% to 1%): Fatigue, weakness, rigors, flushing, taste disturbance, fungemia, pain, chills

Frequency not reported: Discomfort, jitteriness, pneumonia, chapped lips, peripheral edema

Postmarketing reports: Infusion reactions (including tachycardia, wheezing, pyrexia, rigors, systemic flushing, vertigo, syncope, metallic taste)

Serious gram-negative infections (including bloodstream infections) were reported in 10/120 daptomycin-treated patients in the S aureus bacteremia/endocarditis trial compared to 0/115 in comparator-treated patients. Gram-negative infections included cholangitis, alcoholic pancreatitis, sternal osteomyelitis/mediastinitis, bowel infarction, recurrent Crohn's disease, recurrent line sepsis, and recurrent urosepsis.

One patient developed S aureus endocarditis with a 2 cm mitral vegetation, bowel infarction, and polymicrobial bacteremia that ultimately lead to death following mitral valve repair complicated by sternal osteomyelitis.

Pyrexia has also been reported during postmarketing experience.

Respiratory

Common (1% to 10%): Pharyngolaryngeal pain, dyspnea

Frequency not reported: Pleural effusions, sore throat, adenoviral upper respiratory infection, upper respiratory tract infection (not otherwise specified), dyspnea with hypoxic respiratory insufficiency, diffuse pulmonary infiltrates

Postmarketing reports: Cough, eosinophilic pneumonia, organizing pneumonia

Symptoms of eosinophilic pneumonia have included fever, dyspnea with hypoxic respiratory insufficiency, diffuse pulmonary infiltrates, cough, shortness of breath, and difficulty breathing.

Gastrointestinal

Common (1% to 10%): Abdominal pain, diarrhea, gastrointestinal and abdominal pain, nausea, vomiting, constipation, flatulence, bloating and distension

Uncommon (0.1% to 1%): Abdominal distention, stomatitis, dyspepsia, glossitis

Frequency not reported: Dry mouth, epigastric discomfort, gingival pain, oral candidiasis, oral hypoesthesia, loose stools, gastrointestinal hemorrhage, abnormal bowel sounds, aphthous stomatitis

Postmarketing reports: Clostridium difficile-associated diarrhea

Nausea and vomiting have also been reported during postmarketing experience.

Dermatologic

Common (1% to 10%): Pruritus, increased sweating, rash

Uncommon (0.1% to 1%): Eczema, urticaria

Frequency not reported: Heat rash, generalized pruritus, vesicular rash, erythema, cellulitis, papular rash

Postmarketing reports: Serious skin reactions (including Stevens-Johnson syndrome, vesiculobullous rash [with or without mucous membrane involvement]), acute generalized exanthematous pustulosis

Cardiovascular

Common (1% to 10%): Hypertension, hypotension

Uncommon (0.1% to 1%): Supraventricular arrhythmia, supraventricular tachycardia, extrasystole

Frequency not reported: Atrial fibrillation, atrial flutter, cardiac arrest, cardiac failure, cardiac disorders (unspecified)

Nervous system

Common (1% to 10%): Headache, dizziness

Uncommon (0.1% to 1%): Vertigo, paresthesia, taste disorder, tremor

Frequency not reported: Peripheral nervous system events (such as paresthesias, dysesthesias, peripheral neuropathies), tinnitus, dyskinesia

Postmarketing reports: Peripheral neuropathy

Hepatic

Common (1% to 10%): Abnormal liver function tests (increased ALT, increased AST, increased alkaline phosphatase)

Rare (less than 0.1%): Jaundice

Frequency not reported: Hepatobiliary disorder

Genitourinary

Common (1% to 10%): Urinary tract infections

Uncommon (0.1% to 1%): Vaginitis

Frequency not reported: Vaginal candidiasis, fungal urinary tract infection, proteinuria, vaginal discharge, asymptomatic foamy urine

Hematologic

Anemia and thrombocytopenia have also been reported during postmarketing experience.

Common (1% to 10%): Anemia

Uncommon (0.1% to 1%): Leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased INR, thrombocythemia

Rare (less than 0.1%): Prolonged prothrombin time

Frequency not reported: Lymphadenopathy

Postmarketing reports: Decreased platelet count

Local

Common (1% to 10%): Infusion site reactions

Frequency not reported: Injection site reactions, injection site erythema, injection site phlebitis

Metabolic

Uncommon (0.1% to 1%): Hypomagnesemia, increased serum bicarbonate, electrolyte imbalance/disturbance, decreased appetite, hyperglycemia, increased serum lactate dehydrogenase (LDH)

Frequency not reported: Increased blood phosphorous, elevated alkaline phosphatase, hypoglycemia, hypokalemia, hyperkalemia

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity

Postmarketing reports: Anaphylaxis, hypersensitivity reactions (including angioedema, drug rash with eosinophilia and systemic symptoms [DRESS], pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, pulmonary eosinophilia, vesiculobullous rash with mucous membrane involvement, sensation of oropharyngeal swelling)

Ocular

Uncommon (0.1% to 1%): Eye irritation

Frequency not reported: Blurred vision

Postmarketing reports: Visual disturbances

Renal

Renal insufficiency and renal failure have also been reported during postmarketing experience.

Uncommon (0.1% to 1%): Renal impairment (including renal failure, renal insufficiency), increased serum creatinine

Frequency not reported: Renal impairment (including interstitial nephritis, toxic nephropathy, acute prerenal failure, acute or chronic renal failure, renal impairment, renal tubular necrosis), worsening CrCl/decreased renal function

Postmarketing reports: Acute kidney injury

Oncologic

Frequency not reported: Benign and malignant neoplasms (unspecified)