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SPIRAMYCIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Spiramycin is a macrolide antibiotic with chemical, physical, and biologic properties similar to erythromycin. It was isolated from Streptomyces ambofaciens in 1954 (Kucers & Bennett, 1979).
    B) The spectrum of activities of spiramycin includes various gram-positive cocci and bacilli, and gram-negative bacilli (Gaska et al, 1985).

Specific Substances

    1) Foromacidin
    2) Provamycin
    3) Rovamicina
    4) Rovamycin
    5) RP 5337
    6) Selectomycin
    7) Sequamycin
    8) Rovamicina(R) (Italy)
    9) Rovamycine(R) (France)
    10) ACETYLSPIRAMYCIN
    11) ESPIRAMICINA
    12) LEUCOMYCIN

Available Forms Sources

    A) USES
    1) Spiramycin is a macrolide antibiotic used similar to erythromycin in the treatment of susceptible bacterial infections. It has also been used to treat protozoal infections cryptosporidiosis and toxoplasmosis (S Sweetman , 2001).

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) Spiramycin has not been associated with severe adverse effects. Blurred vision, rhinitis, dermatitis, asthma, gastroenteritis, syncope, and paresthesias may occur. QT interval prolongation has been reported in newborn infants with therapeutic use.
    B) WITH POISONING/EXPOSURE
    1) Information on overdose effects of spiramycin is very limited.
    0.2.4) HEENT
    A) WITH THERAPEUTIC USE
    1) Blurred vision and hyperemia, anosmia, and rhinitis may occur with therapeutic use.
    0.2.5) CARDIOVASCULAR
    A) WITH THERAPEUTIC USE
    1) QT interval prolongation has occurred during therapeutic dosing in infants and is considered a rare event.
    0.2.6) RESPIRATORY
    A) WITH POISONING/EXPOSURE
    1) Asthma has been reported in factory workers with occupational exposure to spiramycin powder; presumably due to hypersensitivity.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Paresthesias of the fingertips and syncope have been reported in a few cases of therapeutic use.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Dry mouth, diarrhea, and GI upset have been noted when the drug was taken therapeutically. One case of pseudomembranous colitis was seen.
    0.2.14) DERMATOLOGIC
    A) WITH POISONING/EXPOSURE
    1) Contact dermatitis, eczema, or urticaria may occur from occupational exposure.
    0.2.20) REPRODUCTIVE
    A) Pregnancy Category C
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) No specific laboratory measures are necessary unless clinically indicated.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) The toxic dose of spiramycin is unknown. Theoretically, it appears that ingestions that are several times the therapeutic dose could be ingested without serious effects other than possible gastroenteritis. Activated charcoal may be reserved for amounts greater than this until more overdose information is available. Vomiting may occur spontaneously.
    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) Monitor fluids and electrolytes in those cases where diarrhea and vomiting have been extensive.
    D) QT PROLONGATION
    1) QT prolongation is considered a rare event of spiramycin therapy. There are no reports of torsades de pointes in overdose.
    E) TORSADES DE POINTES: Hemodynamically unstable patients require electrical cardioversion. Treat stable patients with magnesium (first-line agent) and/or atrial overdrive pacing. Correct electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia) and hypoxia, if present.
    1) MAGNESIUM SULFATE/DOSE: ADULT: 1 to 2 grams diluted in 10 milliliters D5W IV/IO over 15 minutes. An optimal dose has not been established. Followed if needed by a second 2 gram bolus and an infusion of 0.5 to 1 gram/hour, if dysrhythmias recur. CHILDREN: 25 to 50 mg/kg diluted to 10 mg/mL; infuse IV over 5 to 15 minutes.
    2) OVERDRIVE PACING: Begin at 130 to 150 beats per minute, decrease as tolerated.
    3) Avoid class Ia (eg, quinidine, disopyramide, procainamide), class Ic (eg, flecainide, encainide, propafenone) and most class III antidysrhythmics (eg, N-acetylprocainamide, sotalol).
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) The toxic dose of spiramycin is unknown. Theoretically, several times the therapeutic dose could be ingested without serious effects other than possible gastroenteritis.
    B) Doses of up to 15 million units have been given daily (divided doses) for severe infections.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Spiramycin has not been associated with severe adverse effects. Blurred vision, rhinitis, dermatitis, asthma, gastroenteritis, syncope, and paresthesias may occur. QT interval prolongation has been reported in newborn infants with therapeutic use.
    B) WITH POISONING/EXPOSURE
    1) Information on overdose effects of spiramycin is very limited.

Heent

    3.4.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Blurred vision and hyperemia, anosmia, and rhinitis may occur with therapeutic use.
    3.4.3) EYES
    A) HYPEREMIA
    1) WITH THERAPEUTIC USE
    a) One study looking at hyperendemic trachoma used a 1% spiramycin ointment. Eighteen of 40 patients developed a reaction in one to three weeks.
    1) The reaction included watering, moderate to severe edema and erythema of the eyelids, moderate discharge, and edema and hyperemia of the bulbar and palpebral conjunctivae. When the ointment was discontinued, the reaction subsided in a week (Darougar et al, 1980).
    B) BLURRED VISION
    1) WITH THERAPEUTIC USE
    a) Blurred vision occurs occasionally with therapeutic use (DeCock & Poels, 1988).
    3.4.5) NOSE
    A) ANOSMIA
    1) WITH POISONING/EXPOSURE
    a) Anosmia was reported in a worker who was routinely handled spiramycin powder, and who had symptoms of asthma (Moscato et al, 1984).
    B) RHINITIS
    1) WITH POISONING/EXPOSURE
    a) Rhinitis has been noted in factory workers exposed to spiramycin (Nava, 1976).

Cardiovascular

    3.5.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) QT interval prolongation has occurred during therapeutic dosing in infants and is considered a rare event.
    3.5.2) CLINICAL EFFECTS
    A) PROLONGED QT INTERVAL
    1) WITH THERAPEUTIC USE
    a) SUMMARY - QT prolongation is considered a rare event during therapeutic use (USPDI, 1999).
    b) CASE REPORT - Stramba-Badiale et al (1997) reported recording ECG before, during and after spiramycin prophylaxis (350,000 IU/kg/day) in 8 newborns, with comparison to 8 controls (no drug therapy). QTc dispersion and QT interval were higher during drug therapy in all 8 infants than after drug withdrawal, and were markedly increased in two infants who also experienced cardiac arrest.
    1) Seven of the 8 treated infants also experienced a thickening of the left ventricular posterior wall, similar to that seen in congenital long QT syndrome, which disappeared after drug withdrawal. It is possible that torsades de pointes could occur and potentially lead to cardiac arrest, especially in an overdose.

Respiratory

    3.6.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Asthma has been reported in factory workers with occupational exposure to spiramycin powder; presumably due to hypersensitivity.
    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) WITH POISONING/EXPOSURE
    a) Asthma has been reported in workers of pharmaceutical factories where they came in contact with spiramycin powder. Cough, dyspnea, chest tightness, and asthma were the primary symptoms, which cleared when they were not exposed for 3 or 4 days.
    1) The reaction was thought to be a hypersensitivity reaction rather than a direct irritant effect (Moscato et al, 1984; Davies & Pepys, 1975; Malo & Cartier, 1988).
    b) CASE REPORT - Frothy sputum was reported in one factory worker who routinely handled (6 to 7 months) spiramycin powder (Moscato et al, 1984).
    c) CASE REPORT - A woman who was exposed to spiramycin in a chicken feed developed symptoms of late asthmatic response and leukocytosis (Paggiaro et al, 1979).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Paresthesias of the fingertips and syncope have been reported in a few cases of therapeutic use.
    3.7.2) CLINICAL EFFECTS
    A) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) Paresthesia of the fingertips has been described in a few cases of therapeutic use (Engelen et al, 1981). This generally occurs after a loading dose, and is of short duration (30 minutes or less). Generally it does not recur(Pilla et al, 1987).
    B) SYNCOPE
    1) WITH THERAPEUTIC USE
    a) Dizziness occurs occasionally with therapeutic use, especially early in therapy (Engelen et al, 1981).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Dry mouth, diarrhea, and GI upset have been noted when the drug was taken therapeutically. One case of pseudomembranous colitis was seen.
    3.8.2) CLINICAL EFFECTS
    A) APTYALISM
    1) WITH THERAPEUTIC USE
    a) Dry mouth was reported infrequently (2 of 48 cases) during therapeutic use (Soekrawinata et al, 1984).
    B) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) THERAPEUTIC - Diarrhea occurs occasionally as a side effect, but it is generally not severe in patients taking therapeutic doses (Engelen et al, 1981).
    C) GASTRITIS
    1) WITH THERAPEUTIC USE
    a) Gastrointestinal upset occurs commonly (up to 20% of patients). Signs and symptoms included nausea, vomiting, dysphagia, upper GI discomfort, diarrhea, abdominal pain, and spastic colitis (Biermann et al, 1982; DeCock & Poels, 1988; (Engelen et al, 1981). Ulcerated esophagitis (i.e., chest pain, heartburn) is a rare adverse event of therapy (USPDI, 1999).
    b) Spiramycin has a lower incidence of gastrointestinal side effects than erythromycin (Pilot & Qin, 1988).
    2) WITH POISONING/EXPOSURE
    a) It is unknown if an overdose produces more of an effect than the gastrointestinal upset seen with therapeutic use.
    D) ANTIBIOTIC ENTEROCOLITIS
    1) WITH THERAPEUTIC USE
    a) One case of pseudomembranous colitis was reported in a series of 105 patients treated with spiramycin (Biermann et al, 1982).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) WITH THERAPEUTIC USE
    a) SUMMARY - Cholestatic hepatitis is considered a rare event of therapeutic spiramycin use (USPDI, 1999). Although hepatitis occurs as a side effect of some macrolide antibiotics, spiramycin does not form cytochrome P-450-nitrosoalkane complexes (Pessayre et al, 1985).

Dermatologic

    3.14.1) SUMMARY
    A) WITH POISONING/EXPOSURE
    1) Contact dermatitis, eczema, or urticaria may occur from occupational exposure.
    3.14.2) CLINICAL EFFECTS
    A) DERMATITIS
    1) WITH THERAPEUTIC USE
    a) SUMMARY - Hypersensitivity reactions described as skin rash and itching are reported infrequently with therapeutic use (USPDI, 1999).
    2) WITH POISONING/EXPOSURE
    a) CASE REPORT - Dermatitis developed in a woman who used a chicken feed containing spiramycin (Paggiaro et al, 1979). Contact dermatitis has been reported in farmers who use the antibiotic (Veien et al, 1980), and in veterinarians (Hjorth & Weismann, 1973). Farmers had eczema on the hands, face, and neck.
    B) URTICARIA
    1) WITH THERAPEUTIC USE
    a) Urticaria has been reported in patients taking therapeutic doses (Suprihati et al, 1984).
    2) WITH POISONING/EXPOSURE
    a) Urticaria has been reported in factory workers exposed while at work (Nava, 1976).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH POISONING/EXPOSURE
    a) Nava (1976) reported an increase in positive skin tests in 41 of 305 workers (13%) who had worked with spiramycin for varying times (2 to 6 months). Thirty-seven of the 41 had symptoms of rhinitis, asthma, or urticaria.

Reproductive

    3.20.1) SUMMARY
    A) Pregnancy Category C
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) In a case-control teratological study of women who had received spiramycin during pregnancy with a control group, no increased risk for congenital anomalies was reported with the use of spiramycin (Czeizel et al, 2000).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    SPIRAMYCINC
    Reference: Briggs et al, 1998
    B) GENERAL
    1) Spiramycin does cross the placenta and reaches concentrations in the placenta up to 5 times higher than in corresponding serum. It is given to pregnant women to decrease the risk of toxoplasmosis to the fetus; the drug is administered throughout pregnancy (USPDI, 1999).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Spiramycin is excreted into breast milk (Briggs et al, 1998).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory measures are necessary unless clinically indicated.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) No specific laboratory measures are necessary unless clinically indicated.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) No specific laboratory measures are necessary unless clinically indicated.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) The toxic dose of spiramycin is unknown. Theoretically, a dose that is several times the therapeutic dose could be ingested without serious effects other than possible gastroenteritis.
    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) SUMMARY
    1) The toxic dose of spiramycin is unknown. Theoretically, it appears that ingestions that are several times the therapeutic dose could be ingested without serious effects other than possible gastroenteritis. Activated charcoal may be reserved for amounts greater than this until more overdose information is available. Vomiting may occur spontaneously.
    B) 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) No specific treatment is indicated. Treatment is symptomatic and supportive.
    B) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Extensive loss of fluids and electrolytes has NOT been reported to date, but overdoses should be monitored for cases where vomiting and diarrhea may be extensive.
    C) TORSADES DE POINTES
    1) SUMMARY: QT prolongation is considered a rare event of spiramycin therapy. There are no reports of torsades de pointes in overdose.
    2) SUMMARY
    a) Withdraw the causative agent. Hemodynamically unstable patients with Torsades de pointes (TdP) require electrical cardioversion. Emergent treatment with magnesium (first-line agent) or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities (ie, hypomagnesemia, hypokalemia, hypocalcemia). Correct hypoxia, if present (Drew et al, 2010; Neumar et al, 2010; Keren et al, 1981; Smith & Gallagher, 1980).
    b) Polymorphic VT associated with acquired long QT syndrome may be treated with IV magnesium. Overdrive pacing or isoproterenol may be successful in terminating TdP, particularly when accompanied by bradycardia or if TdP appears to be precipitated by pauses in rhythm (Neumar et al, 2010). In patients with polymorphic VT with a normal QT interval, magnesium is unlikely to be effective (Link et al, 2015).
    3) MAGNESIUM SULFATE
    a) Magnesium is recommended (first-line agent) for the prevention and treatment of drug-induced torsades de pointes (TdP) even if the serum magnesium concentration is normal. QTc intervals greater than 500 milliseconds after a potential drug overdose may correlate with the development of TdP (Charlton et al, 2010; Drew et al, 2010). ADULT DOSE: No clearly established guidelines exist; an optimal dosing regimen has not been established. Administer 1 to 2 grams diluted in 10 milliliters D5W IV/IO over 15 minutes (Neumar et al, 2010). Followed if needed by a second 2 gram bolus and an infusion of 0.5 to 1 gram (4 to 8 mEq) per hour in patients not responding to the initial bolus or with recurrence of dysrhythmias (American Heart Association, 2005; Perticone et al, 1997). Rate of infusion may be increased if dysrhythmias recur. For persistent refractory dysrhythmias, a continuous infusion of up to 3 to 10 milligrams/minute in adults may be given (Charlton et al, 2010).
    b) PEDIATRIC DOSE: 25 to 50 milligrams/kilogram diluted to 10 milligrams/milliliter for intravenous infusion over 5 to 15 minutes up to 2 g (Charlton et al, 2010).
    c) PRECAUTIONS: Use with caution in patients with renal insufficiency.
    d) MAJOR ADVERSE EFFECTS: High doses may cause hypotension, respiratory depression, and CNS toxicity (Neumar et al, 2010). Toxicity may be observed at magnesium levels of 3.5 to 4.0 mEq/L or greater (Charlton et al, 2010).
    e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respiratory rate, motor strength, deep tendon reflexes, serum magnesium, phosphorus, and calcium concentrations (Prod Info magnesium sulfate heptahydrate IV, IM injection, solution, 2009).
    4) OVERDRIVE PACING
    a) Institute electrical overdrive pacing at a rate of 130 to 150 beats per minute, and decrease as tolerated. Rates of 100 to 120 beats per minute may terminate torsades (American Heart Association, 2005). Pacing can be used to suppress self-limited runs of TdP that may progress to unstable or refractory TdP, or for override refractory, persistent TdP before the potential development of ventricular fibrillation (Charlton et al, 2010). In a case series overdrive pacing was successful in terminating TdP associated with bradycardia and drug-induced QT prolongation (Neumar et al, 2010).
    5) POTASSIUM REPLETION
    a) Potassium supplementation, even if serum potassium is normal, has been recommended by many experts (Charlton et al, 2010; American Heart Association, 2005). Supplementation to supratherapeutic potassium concentrations of 4.5 to 5 mmol/L has been suggested, although there is little evidence to determine the optimal range in dysrhythmia (Drew et al, 2010; Charlton et al, 2010).
    6) ISOPROTERENOL
    a) Isoproterenol has been successful in aborting torsades de pointes that was resistant to magnesium therapy in a patient in whom transvenous overdrive pacing was not an option (Charlton et al, 2010) and has been successfully used to treat torsades de pointes associated with bradycardia and drug induced QT prolongation (Keren et al, 1981; Neumar et al, 2010). Isoproterenol may have a limited role in pharmacologic overdrive pacing in select patients with drug-induced torsades de pointes and acquired long QT syndrome (Charlton et al, 2010; Neumar et al, 2010). Isoproterenol should be avoided in patients with polymorphic VT associated with familial long QT syndrome (Neumar et al, 2010).
    b) DOSE: ADULT: 2 to 10 micrograms/minute via a continuous monitored intravenous infusion; titrate to heart rate and rhythm response (Neumar et al, 2010).
    c) PRECAUTIONS: Correct hypovolemia before using; contraindicated in patients with acute cardiac ischemia (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    1) Contraindicated in patients with preexisting dysrhythmias; tachycardia or heart block due to digitalis toxicity; ventricular dysrhythmias that require inotropic therapy; and angina. Use with caution in patients with coronary insufficiency (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    d) MAJOR ADVERSE EFFECTS: Tachycardia, cardiac dysrhythmias, palpitations, hypotension or hypertension, nervousness, headache, dizziness, and dyspnea (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    e) MONITORING PARAMETERS: Monitor heart rate and rhythm, blood pressure, respirations and central venous pressure to guide volume replacement (Prod Info Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, 2013).
    7) OTHER DRUGS
    a) Mexiletine, verapamil, propranolol, and labetalol have also been used to treat TdP, but results have been inconsistent (Khan & Gowda, 2004).
    8) AVOID
    a) Avoid class Ia antidysrhythmics (eg, quinidine, disopyramide, procainamide, aprindine), class Ic (eg, flecainide, encainide, propafenone) and most class III antidysrhythmics (eg, N-acetylprocainamide, sotalol) since they may further prolong the QT interval and have been associated with TdP.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) The toxic dose of spiramycin is unknown. Theoretically, several times the therapeutic dose could be ingested without serious effects other than possible gastroenteritis.
    B) Doses of up to 15 million units have been given daily (divided doses) for severe infections.

Therapeutic Dose

    7.2.1) ADULT
    A) SUMMARY
    1) Dosing of spiramycin can be expressed as either mg or International Units; 1 mg of spiramycin is equivalent to approximately 3000 International Units (USPDI, 1999).
    2) ADULTS/ADOLESCENTS: 1 to 2 g (3,000,000 to 6,000,000 International Units) 2 times a day; or 500 mg to 1 g (1,500,000 to 3,000,000 International Units) 3 times a day (USPDI, 1999).
    a) SEVERE INFECTIONS: 2 to 2.5 g (6,000,000 to 7,500,000 International Units) 2 times a day (USPDI, 1999).
    B) DISEASE STATE
    1) TOXOPLASMA GONDII: Available only by request from the FDA; used primarily for treatment of acute infection during pregnancy.
    a) FIRST TRIMESTER: 3 g (9,000,000 International Units) per day in divided doses of 3 to 4 (USPDI, 1999).
    b) SECOND OR THIRD TRIMESTER: 25 to 30 mg pyrimethamine/day in combination with 2 to 3 g of sulfadiazine/day and folinic acid 5 mg/day for 3 weeks, alternating with 3 g (9,000,000 International Units) of spiramycin, divided into 3 or 4 doses, for 3 weeks (USPDI, 1999).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) Doses of up to 15 million units have been given daily (divided doses) for severe infections (S Sweetman , 2001).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 322 mg/kg (RTECS, 2001)
    2) LD50- (ORAL)MOUSE:
    a) 2900 mg/kg (RTECS, 2001)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) 1470 mg/kg (RTECS, 2001)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 575 mg/kg (RTECS, 2001)
    5) LD50- (ORAL)RAT:
    a) 3550 mg/kg (RTECS, 2001)
    6) LD50- (SUBCUTANEOUS)RAT:
    a) 1000 mg/kg (RTECS, 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Spiramycin appears to be less active than erythromycin in vitro, but achieves higher tissue levels which increases its effectiveness (Suprihati et al, 1984).
    B) The exact mechanism of action is unknown, but its action is directed at the 50s subunit of the bacterial ribosome. There appears to be interference with translocation at this site (Pilla et al, 1987).

Physicochemical

Physical Characteristics

    A) a white or slightly yellowish, slightly hygroscopic powder (S Sweetman , 2001)

Molecular Weight

    A) 843.1 (S Sweetman , 2001)

References

General Bibliography

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    40) Product Information: Isuprel(TM) intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection, isoproterenol HCl intravenous injection, intramuscular injection, subcutaneous injection, intracardiac injection. Hospira, Inc. (per FDA), Lake Forest, IL, 2013.
    41) Product Information: magnesium sulfate heptahydrate IV, IM injection, solution, magnesium sulfate heptahydrate IV, IM injection, solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2009.
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