Ketek

tapentadol hydrochloride

VibativKetek

Pharmacologic class: Opioid agonist

Therapeutic class: Opioid analgesic

Controlled substance schedule II

Pregnancy risk category C

Pharmacologic class: Lipoglyco-peptide

Therapeutic class: Anti-infective

Pregnancy risk category C

GI: nausea, vomiting, diarrhea, abdominal pain, taste disturbance, Clostridium difficile-associated diarrhea

Pharmacologic class: Ketolide antibiotic

Therapeutic class: Anti-infective

Pregnancy risk category C

FDA Box Warning

Know that Nucynta ER is an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit. Assess each patient's risk of opioid abuse or addiction before prescribing Nucynta ER. Risk of opioid abuse increases in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (such as major depressive disorder). Routinely monitor all patients receiving Nucynta ER for signs and symptoms of misuse, abuse, and addiction during treatment.

Respiratory depression, including fatal cases, may occur with Nucynta ER, even when drug has been used as recommended and not misused or abused. Proper dosing and titration are essential; Nucynta ER should only be prescribed by health care professionals knowledgeable in the use of potent opioids for management of chronic pain. Monitor patients for respiratory depression, especially during initiation of Nucynta ER or after a dosage increase. Instruct patients to swallow tablets whole. Crushing, dissolving, or chewing extended-release tablets can cause rapid release and absorption of a potentially fatal tapentadol dose.

Accidental ingestion of Nucynta ER, especially in children, can result in a fatal tapentadol overdose.

Consuming alcohol with Nucynta ER may result in increased tapentadol plasma level and potentially fatal overdose. Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol while taking Nucynta ER.

Action

Exact mechanism unknown. Analgesic effect may be due to mu-opioid agonist activity and inhibition of norepinephrine reuptake.

Availability

Tablets: 50 mg, 75 mg, 100 mg

Tablets (extended-release): 50 mg, 100 mg, 150 mg, 200 mg, 250 mg

Indications and dosages

Relief of moderate to severe acute pain

Adults ages 18 and older: 50 mg, 75 mg, or 100 mg (immediate-release) P.O. q 4 to 6 hours depending on pain intensity. On day 1, may give second dose as early as 1 hour after initial dose, if needed. Maximum daily dosage on day 1 is 700 mg and on subsequent days, 600 mg. Higher dosages not recommended.

Management of moderate to severe chronic pain and neuropathic pain associated with diabetic peripheral neuropathy when continuous, around-the-clock opioid analgesic is needed for an extended period

Adult: Individualize dosing regimen according to pain severity and previous experience with similar drugs. Initially in patient not currently taking opioid analgesics, 50 mg (extended-release tablets) P.O. b.i.d. q 12 hours. Dosage range is 100 to 250 mg (extended-release tablets) P.O. b.i.d. q 12 hours. Patients receiving immediate-release form may be converted to extended-release by administering same total daily dose at half the total daily immediate-release dose q 12 hours. Maximum daily extended release dosage is 500 mg.

Dosage adjustment

• Moderate hepatic impairment
• Elderly patients

Contraindications

• Hypersensitivity to drug or its components (extended-release form)
• Significant respiratory depression, acute or severe bronchial asthma or hypercapnia in unmonitored settings or in absence of resuscitative equipment
• Paralytic ileus
• Monoamine oxidase (MAO) inhibitor use within last 14 days

Precautions

Use cautiously in:
• severe hepatic or renal impairment (use not recommended)
• moderate hepatic impairment
• respiratory depression, hypoxia, hypercapnia, upper airway obstruction, decreased respiratory reserve (such as asthma, chronic obstructive pulmonary disease, or cor pulmonale), severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, coma, hypotension
• biliary tract disease, including pancreatitis
• head injury, other intracranial injuries, increased intracranial pressure, seizures
• impaired consciousness or coma susceptible to intracranial effects of carbon dioxide retention (avoid extended-release use)
• concurrent use of other CNS depressants or serotonergic agents
• elderly or debilitated patients
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).

Administration

• Administer with or without food. Give extended-release tablets whole.

Don't give concurrently or within 14 days of MAO inhibitor.
• Be aware that extended-release tablets aren't for use as an as-needed analgesic, for pain that is mild or not expected to persist for an extended time, for acute pain, or for postoperative pain unless patient is already receiving long-term opioid therapy.
• Be aware that withdrawal symptoms may occur if extended-release form is discontinued abruptly. Taper dosage to reduce withdrawal symptoms.

Adverse reactions

CNS: dizziness, somnolence, headache, fatigue, tremor, lethargy, insomnia, confusion, abnormal dreams, anxiety, seizures

EENT: nasopharyngitis

GI: nausea, vomiting, constipation, dry mouth, dyspepsia, decreased appetite

GU: urinary tract infection

Musculoskeletal: arthralgia

Respiratory: upper respiratory tract infection, respiratory depression

Skin: rash, pruritus, excessive sweating

Other: hot flushing, physical or psychological drug dependence, drug tolerance, hypersensitivity

Interactions

Drug-drug. Antidepressants, antihistamines, general anesthetics, sedative-hypnotics, other CNS depressants: additive CNS depression leading to potentially life-threatening reactions MAO inhibitors (such as isocarboxazid, phenelzine, tranylcypromine): increased risk of potentially fatal reactions (hyperthermia, myoclonus, autonomic instability)

Mixed agonist or antagonist opioids (such as butorphanol, nalbuphine, pentazocine): reduced analgesic effect; precipitated withdrawal symptoms

Serotonergics (such as MOA inhibitors and triptans, selective norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, other drugs that impair metabolism of serotonin): risk of potentially life-threatening serotonin syndrome

Drug-behaviors. Alcohol use: increased CNS depression

Patient monitoring

Stay alert for overdose signs and symptoms, such as CNS and respiratory depression, GI cramping, and constipation; provide supportive measures as appropriate.
• Monitor vital signs and CNS and respiratory status.
• Assess pain level and efficacy of pain relief.
• Monitor patient for signs and symptoms of drug dependence or tolerance.
• Monitor patient for hypotension during dosage initiation and titration.

Patient teaching

• Instruct patient to take drug with or without food.
• Tell patient to take one extendedrelease tablet at a time with a sufficient amount of water to ensure complete swallowing immediately after placing tablet in the mouth. Tell patient that these tablets must be swallowed whole and must not be split, broken, chewed, dissolved, or crushed.

Instruct patient to stop taking drug and immediately tell prescriber if a seizure occurs.

Caution patient not to stop taking drug suddenly and that drug must be tapered.
• Advise patient to avoid alcohol use while taking drug.
• Advise patient to consult prescriber before taking other prescription or nonprescription drugs.
• Tell patient to notify prescriber if shortness of breath or difficulty breathing occurs or if nausea, vomiting, or constipation become pronounced.
• Instruct patient to move slowly when sitting up or standing to avoid dizziness or light-headedness from sudden blood pressure decrease.
• Caution patient to avoid driving and other hazardous activities until drug's effects on concentration, alertness, vision, coordination, and physical dexterity are known.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and behaviors mentioned above.


telavancin

Vibativ


Pharmacologic class: Lipoglyco-peptide

Therapeutic class: Anti-infective

Pregnancy risk category C

FDABOXED WARNING

Women of childbearing age should have serum pregnancy test before receiving telavancin.

Avoid using telavancin during pregnancy unless potential benefit to patient outweighs potential risk to fetus.

Adverse developmental outcomes observed in three animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans.

Action

Binds to bacterial membrane and disrupts membrane barrier function

Availability

Injection: 250 mg, 750 mg in single-use vials

Indications and dosages

Complicated skin and skin-structure infections caused by susceptible gram-positive bacteria

Adults: 10 mg/kg I.V infusion over 60 minutes q 24 hours for 7 to 14 days

Dosage adjustment

• Renal impairment

Contraindications

None

Precautions

Use cautiously in:
• renal impairment
• concurrent use of drugs known to prolong QT interval
• history of congenital long QT syndrome, known prolongation of QTc interval, uncompensated heart failure, severe left ventricular hypertrophy (avoid use)
• elderly patients
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Obtain renal function studies before starting therapy.
• Administer slowly (over 60 minutes) to reduce risk of infusion-related reactions.
• Although drug doesn't interfere with coagulation, it does, shortly after completion of infusion, interfere with certain tests used to monitor coagulation, such as prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time (aPTT), activated clotting time, and coagulation-based factor Xa tests. Don't collect blood samples for such assays immediately or shortly after infusion completion because such effects dissipate as telavancin concentration decreases.

Adverse reactions

CNS: dizziness

CV: cardiac events

GI: nausea, vomiting, diarrhea, abdominal pain, taste disturbance, Clostridium difficile-associated diarrhea

GU: foamy urine, renal events, nephrotoxicity

Respiratory: respiratory events

Skin: rash, pruritus, infusion-site erythema

Other: rigors, decreased appetite, infectious events, superinfection, infusion-site pain, infusion reactions

Interactions

Drug-diagnostic tests. Activated clotting time, aPTT, coagulation-based factor Xa tests, INR, PT; urine qualitative protein assays: interference with results

Patient monitoring

Be aware that new-onset or worsening renal impairment has occurred in patients taking telavancin. Monitor renal function at 48- and 72-hour intervals during treatment, or more frequently if clinically indicated, and at end of therapy.

Watch for C. difficile-associated diarrhea, which may range in severity from mild diarrhea to fatal colitis; consider discontinuing drug if C. difficile-associated diarrhea occurs.
• Watch for "red-man" syndrome, which can result from rapid infusion. Signs and symptoms include flushing of upper body, hypotension, pruritus, and maculopapular rash on face, neck, trunk, and limbs.

Patient teaching

Instruct patient to tell prescriber if severe diarrhea occurs.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.


telithromycin

Ketek


Pharmacologic class: Ketolide antibiotic

Therapeutic class: Anti-infective

Pregnancy risk category C

 

FDABOXED WARNING

Drug is contraindicated in myasthenia gravis because life-threatening or fatal respiratory failure has occurred in these patients.

Action

Blocks protein synthesis by binding to domains II and V of 23S rRNA of 50S ribosomal subunit. Binding at domain II enables drug to retain activity against gram-positive cocci in resistance mediated by methylases that alter domain-V binding site.

Availability

Tablets (film-coated): 300 mg, 400 mg

Indications and dosages

Mild to moderate community-acquired pneumonia caused by Streptococcus pneumoniae (including multidrug-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae

Adults age 18 and older: 800 mg P.O. daily for 7 to 10 days

Dosage adjustment

• Severe renal impairment, with or without coexisting hepatic impairment

Contraindications

• Hypersensitivity to drug, its components, or macrolide antibiotics
• History of hepatitis or jaundice with previous use of telithromycin or macrolide antibiotics
• Concurrent use of cisapride or pimozide
• Myasthenia gravis

Precautions

Use cautiously in:
• severe renal impairment, hepatic dysfunction, congenital prolongation of QT interval, ongoing proarrhythmic conditions (such as uncorrected hypokalemia or hypomagnesemia), clinically significant bradycardia (use should be avoided)
• concurrent use of some HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin), rifampin, and Class IA or Class III antiarrhythmics (use should be avoided)
• concurrent use of midazolam and other benzodiazepines metabolized by CYP3A4 that undergo high first-pass effect (such as triazolam)
• concurrent use of ergot alkaloid derivatives, metoprolol, or rifampin (use not recommended)
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).

Administration

• Administer tablets whole with or without food.
• Give at least 1 hour before or after theophylline (if prescribed).

Don't give currently with cisapride or pimozide.

Adverse reactions

CNS: headache, dizziness, fatigue, loss of consciousness

CV: prolonged QT interval with increased risk of ventricular arrhythmias and torsades de pointes

EENT: visual disturbances, poor visual accommodation

GI: nausea, vomiting, diarrhea, loose stools, light-colored stools, dysgeusia, anorexia, pseudomembranous colitis (possibly caused by Clostridium difficile)

GU: dark urine

Hepatic: abnormal hepatic function, fulminant hepatitis, hepatic necrosis, hepatic failure

Skin: pruritus

Other: superinfection, hypersensitivity reactions including angioedema and anaphylaxis (rare), acute myasthenia gravis exacerbation

Interactions

Drug-drug. Atorvastatin, lovastatin, simvastatin: increased blood levels of these drugs, increased myopathy risk

Benzodiazepines metabolized by CYP3A4 (such as midazolam, triazolam): increased blood levels of these drugs

Cisapride, pimozide: increased blood levels of these drugs, increasing risk of significantly prolonged QT interval

Class IA antiarrhythmics (such as procainamide, quinidine), Class III antiarrhythmics (such as dofetilide): interference with antiarrhythmic efficacy

Colchicine: increased serum colchicine blood level and toxicity risk

Cyclosporine, sirolimus, tacrolimus: increased blood levels of these drugs, with increased toxicity risk CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifampin): subtherapeutic telithromycin blood level CYP3A4 inhibitors (such as itraconazole, ketoconazole): increased telithromycin blood level

Digoxin: increased peak and trough digoxin levels

Ergot alkaloid derivatives (such as dihydroergotamine, ergotamine): acute ergot toxicity

Hexobarbital: increased hexobarbital blood level and toxicity risk

Metoprolol: increased metoprolol effect

Oral anticoagulants: possible potentiation of these drugs

Sotalol: decreased sotalol absorption

Theophylline: increased theophylline blood level, with exacerbated adverse GI reactions

Verapamil: increased verapamil blood level, causing increased risk of cardiotoxicity

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase: increased levels

Patient monitoring

• Monitor liver function tests frequently.

Discontinue drug permanently if patient develops clinical hepatitis or transaminase elevations and other systemic symptoms.
• Monitor patient closely for adverse GI reactions, especially diarrhea.
• In patients receiving drug concurrently with anticoagulants, stay alert for potentiation of anticoagulant effects.
• In patients receiving drug concurrently with midazolam, stay alert for need to adjust midazolam dosage.
• In patients receiving drug concurrently with digoxin, monitor peak and trough digoxin levels periodically, and stay alert for adverse reactions to digoxin.

Patient teaching

• Ensure that patient has received and read medication guide that comes with drug.
• Instruct patient to take tablet whole with or without food.
• Advise patient to take drug at least 1 hour before or after theophylline (if prescribed).
• Stress importance of completing full course of therapy, even if patient feels better.

Urge patient to immediately stop taking drug and report signs and symptoms of liver damage, such as nausea, fatigue, appetite loss, yellowing of skin or eyes, dark urine, light-colored stools, itching, and tender abdomen.

Instruct patient to immediately report fainting episodes or signs of heartbeat irregularities.

Urge patient to immediately report watery or loose stools even as late as several months after taking the last dose.

Advise patient to immediately report itching, throat swelling, and other signs or symptoms of allergic reaction.
• Inform patient that drug may cause visual disturbances.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects vision and alertness.
• Advise patient to consult prescriber before taking other prescription or over-the-counter drugs or dietary supplements.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

telithromycin

(te-lith-roe-mye-sin) ,

Ketek

(trade name)

Classification

Therapeutic: anti infectives
Pharmacologic: ketolides
Pregnancy Category: C

Indications

Community-acquired pneumonia.

Action

Blocks bacterial protein synthesis at the level of the 50S ribosomal subunit.

Therapeutic effects

Resolution of infection.
Active against the following organisms: Staphylococcus aureus (methicillin and erythromycin susceptible strains only), Streptococcus pneumoniae (including multidurg-resistant strains), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, and Mycoplasma pneumoniae.

Pharmacokinetics

Absorption: 57% absorbed following oral administration; unaffected by food.
Distribution: Concentrates in bronchial mucosa, epithelial lining fluid and alveolar macrophages.
Metabolism and Excretion: 70% metabolized by the liver (50% by CYP3A4), 13% excreted unchanged in urine, 7% excreted unchanged via biliary/intestinal elimination.
Half-life: 10 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POrapid1 hr24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; History of hepatitis or jaundice associated with use of telithromycin; Hypersensitivity to macrolides (erythromycin, azithromycin, clarithromycin); Concurrent use of pimozide, ergot alkaloids, simvastatin, lovastatin, atorvastatin, or rifampin; Congenital QTc prolongation, uncorrected hypokalemia or hypomagnesemia, bradycardia, concurrent use of Class IA (quinidine, procainamide) or Class III antiarrhythmics (dofetilide); Concurrent use of colchicine in patients with renal or hepatic impairment; Myasthenia gravis; Lactation: Excreted in breast milk; consider alternative to breastfeeding.
Use Cautiously in: CCr <30 mL/min (dosage not established); Concurrent use of midazolam and other benzodiazpines; Obstetric: Use only if benefits outweigh risks to fetus; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • confusion
  • hallucinations
  • loss of consciousness

Ear, Eye, Nose, Throat

  • visual disturbances

Cardiovascular

  • arrhythmias
  • QTc interval prolongation

Gastrointestinal

  • pseUdomembranous colitis (life-threatening)
  • diarrhea (most frequent)
  • hepatitis
  • HEPATotoxicity (life-threatening)
  • nausea

Neurologic

  • exacerbation of myasthenia gravis

Interactions

Drug-Drug interaction

Blood levels are ↑ by ketoconazole and itraconazole.↑ levels and risk of myopathy from simvastatin, lovastatin, and atorvastatin ; avoid concurrent use.↑ levels and risk of toxicity with colchicine ; avoid concurrent use in patients with renal or hepatic impairment; ↓ dose of colchicine if patients have normal renal and hepatic function.↑ levels and risk of excessive sedation with midazolam ; careful titration is required. Similar effects may occur with triazolam.↑ levels of metoprolol ; use caution in patients with HF.May also ↑ levels, effects and risk of toxicity from ergot derivatives (ergotamine, dihydroergotamine ); concurrent use not recommended; similar effects may occur with carbamazepine, cyclosporine, tacrolimus, sirolimus, hexobarbital, or phenytoin.Rifampin ↓ levels and effectiveness; avoid concurrent use. Similar effects may occur with phenytoin, carbamazepine, or phenobarbital.

Route/Dosage

Oral (Adults) community-acquired pneumonia—800 mg once daily for 7–10 days.

Availability

Tablets: 300 mg, 400 mg

Nursing implications

Nursing assessment

  • Assess for infection (vital signs; sputum, WBC) at beginning of and during therapy.
  • Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
  • Determine any family history of QTc prolongation or proarrythmic conditions (hypokalemia, bradycardia).
  • Monitor for signs or symptoms of hepatitis (fatigue, malaise, anorexia, nausea, jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly). If these occur, discontinue telithromycin immediately and monitor liver function; do not re-administer telithromycin.
  • Lab Test Considerations: May cause ↑ platelet count.
    • Monitor liver function periodically during therapy and if signs of hepatitis occur.

Potential Nursing Diagnoses

Risk for infection (Indications)
Noncompliance (Patient/Family Teaching)

Implementation

  • Oral: Administer with or without food. Swallow tablets whole; do not crush, break, or chew.

Patient/Family Teaching

  • Instruct patient to take medication as directed and to finish medication completely, even if feeling better. Take missed doses as soon as remembered, but do not take more than one dose in a 24–hr period. Advise patient to read Patient Information Sheet prior to starting therapy.
  • May cause visual disturbances (blurred vision, difficulty focusing, diplopia). Caution patient to avoid driving or other activities requiring visual acuity until response to medication is known. Advise patient to notify health care professional if visual disturbances interfere with daily activities.
  • Instruct patient to notify health care professional if fainting occurs.
  • Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools).
  • Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
  • Advise patient to discontinue telithromycin and notify health care professional immediately if signs of liver injury (nausea, fatigue, anorexia, jaundice, dark urine, light-colored stools, pruritus, or tender abdomen) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.

Evaluation/Desired Outcomes

  • Resolution of the signs and symptoms of infection. Length of time for complete resolution depends on the organism and site of infection.

Ketek

a trademark for telithromycin.
References in periodicals archive ?
For antibiotics is very high, partly due to a scandal over the approval of Sanofi's drug Ketek in 2004, which US officials said later should be reserved for serious diseases due to the risk of side effects.
After 13 weeks of dosing, multinucleated hepatocytes were reported for clarithromycin while Ketek elicited increased LFTs, increased NAGs (3x) in urine and phospholipidosis (FDA Briefing Package, 2001).
Other drugs deemed too unsafe for marketing-yet approved--include the type 2 diabetes drag Avandia (linked to heart attack by FDA Medical Reviewer Robert Misbin and likewise so identified in a meta-analysis published in the New England Journal of Medicine); the antibiotic Ketek (inked to liver damage by FDA Medical Reviewer David Ross, who testified that the drug "could kill people from liver damage"); and the antidepressant drugs Paxil, Zoloft, and Effex or (linked to increased risk of suicidality by FDA Medical Reviewer Andrew Mosholder).
McGarity, Corporate Accountability for Scientific Fraud: Ketek and the Perils of Aggressive Agency Preemption, 58 EMORY L.
David Ross, a former Food and Drug Administration (FDA) scientist, described a pattern of political interference in his work that culminated in his resignation after the approval of the antibiotic drug Ketek.
for several drugs, including Avandia, Epogen, Aranesp, and Ketek.
The committee's oversight subcommittee is investigating whether FDA Commissioner Andrew von Eschenbach gave misleading testimony on Sanofi-Aventis SA's antibiotic Ketek during a committee hearing in March.
Telithromycin, which is marketed by Sanofi-Aventis as Ketek, is no longer approved to treat acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis.
More recently we have learned about the potential problems with Ketek, an antibiotic used to treat chronic bronchitis, acute bacterial sinusitis and community acquired pneumonia, including pneumonia caused by resistant strep infections.
Ketek has been linked to rare reports of acute liver failure that have resulted in several deaths and several patients needing a liver transplant.
The nine others are Asep Suryaman, 72, Boengkoes, 71, Natanael Marsudi, 71, Sri Suhardjo, 70, Suryabrata, 71, Isnanto, 76, Buyung Ketek, 52, Markus Giroth, 61, and Sido, 55.