Daptomycin

Daptomycin may be found in some form under the following brand names:

• Cubicin

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• statin medications used to lower cholesterol such as simvastatin (Zocor), atorvastatin (Lipitor), pitavastatin (Livalo), rosuvastatin (Crestor), lovastatin (Mevacor), or pravastatin (Pravachol)

This is not a complete list of daptomycin drug interactions. Ask your doctor or pharmacist for more information.

Call your doctor for instructions if you miss a dose of daptomycin.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Contraindications

• Known hypersensitivity to daptomycin.1 23 24 25

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity, including anaphylaxis and other life-threatening reactions, reported in patients receiving daptomycin.1 23 24 25

Postmarketing reports of angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), pruritus, urticaria, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia (see Eosinophilic Pneumonia under Cautions).1 23 24 25

If hypersensitivity reaction occurs, discontinue daptomycin and initiate appropriate therapy.1 23 24 25

Musculoskeletal Effects

Myopathy, defined as muscle aching or muscle weakness, in conjunction with increased serum CK concentrations up to 10 times ULN reported in patients receiving daptomycin.1 23 24 25 Rhabdomyolysis, with or without renal failure, also reported.1 23 24 25

Monitor for development of muscle pain or weakness, particularly of distal extremities.1 23 24 25 Determine serum CK concentrations weekly during daptomycin treatment;1 23 24 25 monitor more frequently than once weekly in those who develop increases in serum CK concentrations and in those previously or concomitantly treated with an HMG-CoA reductase inhibitor (statin).1 23 24 25 Also monitor serum CK concentrations and renal function more frequently than once weekly in patients with renal impairment.1 23 24 25

Discontinue daptomycin in patients with unexplained signs or symptoms of myopathy in conjunction with increases in CK >1000 U/L (i.e., approximately 5 times ULN) or in patients without reported symptoms who have substantial increases in serum CK concentrations (i.e., >2000 U/L [≥10 times ULN]).1 23 24 25

Elevated serum CK concentrations reported more frequently if daptomycin given more frequently than once daily in clinical trials;1 do not administer more frequently than once daily.1 23 24 25

Consider temporarily discontinuing drugs associated with rhabdomyolysis (e.g., HMG-CoA reductase inhibitors) during daptomycin treatment.1 23 24 25 (See Specific Drugs under Drug Interactions.)

Eosinophilic Pneumonia

Eosinophilic pneumonia reported in some patients receiving daptomycin.1 7 8 9 10 11 16 23 24 25 Patients generally developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates 2–4 weeks after the drug was initiated.1 7 8 9 10 11 16 23 24 25 Improvement or resolution of symptoms generally occurred when daptomycin was discontinued;1 7 8 9 10 11 16 23 24 25 most patients received treatment with systemic corticosteroids.1 7 8 9 10 11 16 23 24 25 Reinitiation of daptomycin has resulted in recurrence of eosinophilic pneumonia.1 7 8 11 23 24 25

FDA determined that there appears to be a temporal association between daptomycin and development of eosinophilic pneumonia;7 some were receiving the drug for non-FDA-labeled uses.7 8 9 Consider that eosinophilic pneumonia can progress to respiratory failure and is potentially fatal if not quickly recognized and appropriately managed.7 8 9 11

Closely monitor for signs and symptoms of eosinophilic pneumonia (e.g., new onset or worsening fever, dyspnea, difficulty breathing, new pulmonary infiltrates).1 7 8 9 10 11 16 23 24 25

Immediately discontinue daptomycin if there are any signs or symptoms of eosinophilic pneumonia.1 7 8 9 10 11 16 23 24 25 Initiate prompt medical evaluation;1 7 8 9 10 11 16 23 24 25 treatment with systemic corticosteroids is recommended.1 8 9 10 11 16 23 24 25

Nervous System Effects

Postmarketing reports of peripheral neuropathy in patients receiving daptomycin;1 23 24 25 be alert to possible manifestations of neuropathy.1 23 24 25

Persisting or Relapsing Staphylococcus aureus Bacteremia/Endocarditis

Treatment failure due to persisting or relapsing S. aureus infection has occurred in patients receiving daptomycin;1 22 23 24 25 fatalities reported.22 S. aureus with reduced susceptibility or resistance to daptomycin have been reported and have emerged during treatment with the drug.1 19 20 21 22 23 24 25

In a clinical study in patients with bacteremia, 16% of daptomycin-treated patients and 10% of patients receiving a comparator anti-infective (vancomycin or a penicillinase-resistant penicillin) had persisting or relapsing S. aureus infections.1 22 23 24 25 In vitro studies indicated reduced susceptibility to daptomycin developed during or following treatment.1 22 23 24 25 Most patients with persisting or relapsing infections had deep-seated infections and did not receive necessary surgical intervention.1 22 23 24 25

Perform repeat blood cultures in patients with persisting or relapsing infection or with poor clinical response.1 23 24 25 If cultures are positive for S. aureus, perform in vitro susceptibility testing using standardized MIC procedures.1 23 24 25 Also perform diagnostic evaluation to rule out sequestered foci of infection.1 23 24 25 Surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or a change in anti-infective regimen may be required.1 23 24 25

Reduced Efficacy in Patients with Moderate Renal Impairment

In a subgroup analysis of a phase 3 clinical study in patients with S. aureus bacteremia/endocarditis, clinical success rate in daptomycin-treated patients with baseline Clcr 30 to <50 mL/minute was only 14% and was lower than that observed in those with baseline Clcr 50–80 or >80 mL/minute (46 or 60%, respectively).1 23 24 25 Decreased clinical success rates to this extent not observed in patients receiving comparator anti-infectives.1 23 24 25

Although only limited data available from phase 3 clinical studies in patients with complicated skin and skin structure infections, clinical success rate in daptomycin-treated patients with Clcr 30 to <50 mL/minute was 47% compared with clinical success rate of 66% in those with Clcr 50–70 mL/minute.1 23 24 25

Consider these efficacy data when selecting anti-infective treatment for patients with baseline moderate to severe renal impairment.1 23 24 25

Tests Used to Monitor Coagulation

Daptomycin causes concentration-dependent false prolongation of the PT and elevated INR if certain recombinant thromboplastin reagents are used for these tests.1 23 24 25

Minimize interference with PT/INR testing by drawing blood specimens for coagulation tests near time of trough plasma daptomycin concentrations; consider that trough plasma concentrations still may be high enough to interfere with such testing.1 23 24 25

If abnormally elevated PT/INR tests occur in a patient receiving daptomycin, repeat coagulation testing using blood specimens drawn just prior to next daptomycin dose (i.e., at trough concentrations).1 23 24 25 If these results remain substantially elevated over what would otherwise be expected, consider alternative methods of measuring PT/INR.1 23 24 25 Also evaluate patient for other causes of abnormally elevated PT/INR.1 23 24 25

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.1 23 24 25 Monitor carefully; institute appropriate therapy if superinfection occurs.1 23 24 25

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 12 14 15 23 24 25 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including daptomycin, and may range in severity from mild diarrhea to fatal colitis.1 12 14 15 23 24 25 C. difficile produces toxins A and B which contribute to development of CDAD;1 12 23 24 25 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1 23 24 25

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.1 12 14 15 23 24 25 Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.1 23 24 25

If CDAD is suspected or confirmed, anti-infectives not directed against C. difficile should be discontinued.1 23 24 25 Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.1 12 14 15 23 24 25

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of daptomycin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1 23 24 25

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.1 23 24 25 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.1 23 24 25

Do not use for treatment of pneumonia.1 23 24 25

Safety and efficacy not studied in patients with prosthetic valve endocarditis.1 23 24 25

Specific Populations

Category B.1 23 24 25

Use during pregnancy only if potential benefits outweigh possible risks to fetus.1 23 24 25

Distributed into human milk.1 23 24 25 (See Distribution under Pharmacokinetics.)

Use with caution in nursing women.1 23 24 25

Safety and efficacy in pediatric patients not established.1 23 24 25

Avoid use in children <12 months of age because of potential risk of adverse muscular, neuromuscular, peripheral nervous system, and CNS effects;1 23 24 25 such effects observed in neonatal dogs receiving IV daptomycin.1 23 24 25

In clinical studies, success rates were lower and incidence of treatment-emergent adverse effects were higher in patients ≥65 years of age compared with younger adults.1 23 24 25

Daptomycin exposures are higher in healthy geriatric adults than in healthy young adults;1 23 24 25 however, daptomycin dosage adjustments not needed in geriatric patients based solely on age.1 23 24 25

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary.1 23 24 25 (See Renal Impairment under Dosage and Administration.)

Pharmacokinetics not altered in patients with moderate hepatic impairment (Child-Pugh class B);1 23 24 25 not studied in patients with severe hepatic impairment.1 23 24 25

Decreased clearance and increased AUC and half-life in patients with renal impairment.1 23 24 25

Monitor renal function and serum CK concentrations more frequently than once weekly in patients with renal insufficiency.1 23 24 25

Dosage adjustments recommended in patients with Clcr <30 mL/minute.1 23 24 25 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Complicated skin and skin structure infections: Diarrhea, nervous system effects (headache, dizziness), rash, abnormal liver function test results, CK elevations, urinary tract infections, hypotension, dyspnea.1 23 24 25

Bacteremia and endocarditis: Abdominal pain, insomnia, pharyngolaryngeal pain, infections (sepsis, bacteremia), chest pain, edema, pruritus, increased sweating, CK elevations, hypotension.1 23 24 25

Does not inhibit or induce CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4; pharmacokinetic interactions with drugs metabolized by these CYP isoenzymes unlikely.1 23 24 25

Specific Drugs and Laboratory Tests

• If you have an allergy to daptomycin or any other part of daptomycin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Obesity: Plasma clearance was 15% and 23% lower and AUC increased by 30% and 31% in moderately obese patients and extremely obese patients, respectively, compared with nonobese controls.

Administer as an IV infusion over 30 minutes (children and adolescents 7 to 17 years of age and adults) or 60 minutes (children 1 to 6 years of age). May also administer IV push over 2 minutes in adults only; do not administer IV push to pediatric patients. Do not use in conjunction with ReadyMED® elastomeric infusion pumps (Cardinal Health, Inc) due to an impurity (2-mercaptobenzothiazole) leaching from the pump system into the daptomycin solution.

HMG-CoA Reductase Inhibitors: May enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification

Monitor signs and symptoms of infection. CPK should be monitored at least weekly during therapy; more frequent monitoring if current or prior statin therapy, unexplained CPK increases, and/or renal impairment. Monitor for muscle pain or weakness, especially if noted in distal extremities. Monitor for new onset or worsening peripheral neuropathy. Monitor for signs/symptoms of eosinophilic pneumonia.