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TROLEANDOMYCIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Troleandomycin, a macrolide antibiotic, is a synthetic derivative of the acetylated ester of oleandomycin.

Specific Substances

    1) Triacetyl ester of oleandomycin
    2) Triacetyloleandomycin
    3) Troleandomycin
    4) CAS 2751-09-9

Available Forms Sources

    A) FORMS
    1) Troleandomycin is available as a 250 mg capsule (equivalent to 250 mg of oleandomycin) (Prod Info TAO(R), troleandomycin, 1995)
    B) USES
    1) Troleandomycin is indicated in the treatment of pneumococcal pneumonia due to susceptible strains of Diplococcus pneumonia. It is also used for the treatment of Group A beta-hemolytic streptococcal infections of the upper respiratory tract (Prod Info TAO(R), troleandomycin, 1995).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Reversible cholestatic jaundice may be noted following chronic ingestion (more than 2 weeks) or repeated courses of therapeutic doses.
    B) WITH POISONING/EXPOSURE
    1) Acute overdosage does not appear to result in severe toxicity. Signs and symptoms appear to be referrable to the gastrointestinal tract and include nausea and vomiting.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, diarrhea, and abdominal cramping may be noted.
    0.2.9) HEPATIC
    A) WITH THERAPEUTIC USE
    1) Hepatotoxicity with transient disturbances of liver function and cholestatic jaundice, accompanied by right upper quadrant pain, gastrointestinal disturbances, eosinophilia, and leukocytosis may be noted following 2 weeks of therapy or repeated courses.
    0.2.20) REPRODUCTIVE
    A) TROLEANDOMYCIN is in pregnancy category C.

Laboratory Monitoring

    A) Plasma troleandomycin levels are not clinically useful for toxicity monitoring. They are rarely available in most clinical sites.
    B) Monitor liver function tests in patients with signs and symptoms of hepatitis. No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Severe toxicity following acute overdosage is unlikely.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    C) CHOLESTATIC JAUNDICE generally resolves with withdrawal of drug therapy. Permanent liver injury is not noted.
    D) Patients developing liver failure should be treated symptomatically and supportively.

Range Of Toxicity

    A) Severe toxicity following acute overdosage is unlikely.
    B) Transient elevation of liver enzymes may be noted following chronic ingestion (more than 2 weeks) or repeated courses of therapeutic doses and resolves with withdrawal of drug therapy.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Reversible cholestatic jaundice may be noted following chronic ingestion (more than 2 weeks) or repeated courses of therapeutic doses.
    B) WITH POISONING/EXPOSURE
    1) Acute overdosage does not appear to result in severe toxicity. Signs and symptoms appear to be referrable to the gastrointestinal tract and include nausea and vomiting.

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, diarrhea, and abdominal cramping may be noted.
    3.8.2) CLINICAL EFFECTS
    A) GASTROENTERITIS
    1) WITH THERAPEUTIC USE
    a) Nausea, vomiting, and diarrhea may occur infrequently with therapeutic doses (Prod Info TAO(R), troleandomycin, 1996).
    B) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) Abdominal cramping and discomfort may occur and is dose-related (Prod Info TAO(R), troleandomycin, 1996).

Hepatic

    3.9.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hepatotoxicity with transient disturbances of liver function and cholestatic jaundice, accompanied by right upper quadrant pain, gastrointestinal disturbances, eosinophilia, and leukocytosis may be noted following 2 weeks of therapy or repeated courses.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) CASE SERIES - Two patients, involved in a safety and efficacy study of low-dose troleandomycin, experienced elevated liver enzyme levels.
    1) In one patient, liver enzyme levels increased 2 weeks after initiating therapy with a combination of troleandomycin and methylprednisolone. The enzyme levels spontaneously decreased to normal levels after reaching a peak of 44 IU/L for SGOT and 194 IU/L for SGPT (Kamada et al, 1993).
    B) CHOLESTATIC HEPATITIS
    1) WITH THERAPEUTIC USE
    a) Cholestatic jaundice and transient disturbances of liver function may occur after 2 weeks of administration or after repeated courses of troleandomycin. The jaundice may be accompanied by right upper quadrant pain, fever, leukocytosis, and eosinophilia (Prod Info TAO(R), troleandomycin, 1995).
    b) Coadministration of oral contraceptive agents has been suggested to increase the risk of cholestatic jaundice (Miguet et al, 1980). Although generally transient, one case report has documented prolonged cholestasis (Larrey et al, 1987).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) WITH THERAPEUTIC USE
    a) Leukocytosis and eosinophilia have been reported to accompany troleandomycin- associated cholestatic jaundice (Prod Info TAO(R), troleandomycin, 1996).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH THERAPEUTIC USE
    a) Anaphylactic-type hypersensitivity may develop with troleandomycin administration (Prod Info TAO(R), troleandomycin, 1996).

Reproductive

    3.20.1) SUMMARY
    A) TROLEANDOMYCIN is in pregnancy category C.
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    TROLEANDOMYCINC
    Reference: Briggs et al, 1998.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma troleandomycin levels are not clinically useful for toxicity monitoring. They are rarely available in most clinical sites.
    B) Monitor liver function tests in patients with signs and symptoms of hepatitis. No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise indicated.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Routine liver functions, including SGOT, bilirubin and alkaline phosphatase during prolonged therapy (more than 2 weeks) or if repeated courses are administered.

Treatment

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Severe toxicity following acute overdosage is unlikely.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Withdrawal of the drug generally results in gradual resolution of the cholestatic jaundice without permanent liver damage (Pessayre et al, 1985; Larrey et al, 1987).
    2) Monitor hepatic function.
    3) Patients developing liver failure should be treated symptomatically.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Plasma troleandomycin levels are not clinically useful for toxicity monitoring. They are rarely available in most clinical sites.
    B) Monitor liver function tests in patients with signs and symptoms of hepatitis. No specific lab work (CBC, electrolytes, urinalysis) is needed unless otherwise indicated.

Range Of Toxicity

Summary

    A) Severe toxicity following acute overdosage is unlikely.
    B) Transient elevation of liver enzymes may be noted following chronic ingestion (more than 2 weeks) or repeated courses of therapeutic doses and resolves with withdrawal of drug therapy.

Therapeutic Dose

    7.2.1) ADULT
    A) Troleandomycin is indicated in the treatment of INFECTIONS caused by susceptible strains of S pyogenes, Diplococcus pneumoniae, and Group A hemolytic Beta-hemolytic streptococci (Prod Info Tao(R), 1995). However, because other less toxic and more effective agents are available, troleandomycin is rarely used for this indication.
    B) Effective in eradicating streptococci from the nasopharynx; however, the no efficacy has been established for troleandomycin in preventing rheumatic fever (Prod Info Tao(R), 1995)
    C) The usual dose of troleandomycin for treating bacterial infections is 250 to 500 mg 4 times daily for adults. For children, the usual dose is troleandomycin 125 to 250 mg (6.6 to 11 mg/kg) every 6 hours (Prod Info Tao(R), 1995).
    7.2.2) PEDIATRIC
    A) Troleandomycin is indicated in the treatment of INFECTIONS caused by susceptible strains of S pyogenes, Diplococcus pneumoniae, and Group A hemolytic Beta-hemolytic streptococci (Prod Info Tao(R), 1995). However, because other less toxic and more effective agents are available, troleandomycin is rarely used for this indication.
    B) Effective in eradicating streptococci from the nasopharynx; however, the no efficacy has been established for troleandomycin in preventing rheumatic fever (Prod Info Tao(R), 1995).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)MOUSE:
    a) >5 g/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) This is a macrolide antibiotic related to erythromycin but generally felt to be less effective and more toxic.
    B) Recent studies have suggested usefulness for severe chronic asthma, it appears to decrease the metabolism of theophylline, thereby increasing theophylline level, perhaps without any antiasthmatic effect of its own.

Physicochemical

Physical Characteristics

    A) Troleandomycin is a white, odorless, crystalline powder. Troleandomycin 1.18 grams is approximately equivalent to 1 gram of oleandomycin (Sweetman, 2001).

Ph

    A) A 10% solution in alcohol (50%) has a pH of 7 to 8.5 (Sweetman, 2001).

Molecular Weight

    A) 814

References

General Bibliography

    1) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    2) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    3) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    4) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    5) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    6) Flotte TR & Loughlin GM: Benefits and complications of troleandomycin (TAO) in young children with steroid-dependent asthma. Pediatr Pulmonol 1991; 10:178-182.
    7) Franco A, Bourlard P, & Massot C: Acute ergotism caused by dihydroergotamine-triacetyloleandomycin association (letter). Nouv Presse Med 1978; 7:205.
    8) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    9) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    10) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    11) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    12) Kamada AK, Hill MR, & Ikle DN: Efficacy and safety of low-dose troleandomycin therapy in children with severe, steroid-requiring asthma. J Allergy Clin Immunol 1993; 91:873-882.
    13) Larrey D, Amouyal G, & Danan G: Prolonged cholestasis after troleandomycin-induced acute hepatitis. J Hepatol 1987; 4:327-329.
    14) Miguet JP, Vuitton D, & Passayre D: Jaundice from troleandomycin and oral contraceptives (letter). Ann Intern Med 1980; 92:434.
    15) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    16) Pessayre D, Larrey D, & Funck-Brentano C: Drug interactions and hepatitis produced by some macrolide antibiotics. J Antimicrob Chemother 1985; 16(Suppl A):181-194.
    17) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    18) Product Information: Letter to prescribers. Marion Merrell Dow, Kansas City, MO, 1992.
    19) Product Information: TAO(R), troleandomycin. Roerig, 1996.
    20) Product Information: TAO(R), troleandomycin. Pfizer Inc, 1995.
    21) Product Information: Tao(R), troleandomycin. Roerig, New York, NY, 1995.
    22) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    23) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    24) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.