Spiramycin

785.96

842.513977

232-429-6

DTXSID9023594|DTXSID6045402

Amorphous

J - Antiinfectives for systemic use

29419090

195

3.06

white to light yellow

1.2±0.1 g/cm3

126-128 °C

914℃

>110°(230°F)

1.550

soluble in methanol. Slightly soluble in water;ethanol: 50 mg/mL, clear to slightly hazy, light-yellow

2-8°C

9.9X10-31 mm Hg at 25 °C (est)

LD50 in rats (mg/kg): 9400 orally; 1000 s.c.; 170 i.v. (Sous)

D20 -80° (methanol)

Base

Henry's Law constant = 9.0X10-35 atm-cu m/mol at 25 °C (est)

pKa1 = 7.88; pKa2 = 9.28 (est)

MW: 843.05. Crystals. MP: 134-137 °C. Specific optical rotation: -96 deg at 20 °C/D /Spiramycin I/|Crystals. MP: 140-143 °C. Specific optical rotation: -92.5 deg at 20 °C/D /Spiramycin I triacetate/|MW: 885.10. Crystals. MP: 130-133 °C. Specific optical rotation: -86 deg at 20 °C/D /Spiramycin II/|Crystals from cyclohexane. MP: 156-160 °C. Specific optical rotation: -98.4 deg at 20 °C/D /Spiramycin II diacetate/|MW: 899.11. Crystals. MP: 128-131 °C. Specific optical rotation: -83 deg at 20 °C/D /Spiramycin III/|Crystals from cyclohexane. MP: 140-142 °C. Specific optical rotation: -90.4 deg at 20 °C/D /Spiramycin III diacetate/

NONH for all modes of transport

1

36/37/38

26-36-24/25

WG9400000

Xi

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Incompatible materials: Strong oxidizing agents

|Danger|H315 (33.33%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P272, P273, P280, P285, P302+P352, P304+P340, P304+P341, P305+P351+P338, P312, P321, P332+P313, P333+P313, P337+P313, P342+P311, P362, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 8 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place., The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Skin protection: Handle with gloves.|Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.|Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Precautions for safe handling: Avoid formation of dusts and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for proventive fire protection.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

In influent and effluent sewage treatment plant samples from six locations in Italy, spiramycin was found at not detected to 47 (4.8 median) and 12-418 (35 median) mg/day/1000 inhabitants, respectively; samples were collected in Naples, Latina and Cuneo Jan-Mar 2004, Cagliari and Varese Lago Jun-Sep 2004 and Varese Olona Jan-Mar and Jun-Sep 2004(1). Spiramycin was detected in 6 of 8 influent samples at 0.0092-0.16 ug/L and 4 of 8 effluent samples at 0.0038-0.032 ug/L from 8 sewage treatment plants in Beijing, China; spiramycin was detected in 83% of 35 sewage sludge samples from the same plants at a mean, median and maximum concentration of 7.8, 7.0 and 32 ug/kg dry weight, respectively; samples were collected Jan 15, May 28, Sep 24, 2008, Oct 15, 2009 and May 13, 2010(2).

IDENTIFICATION AND USE: Spiramycin is a macrolide antibiotic used for the treatment and control of a number of bacterial and mycoplasmal infections in animals. It is available as a spiramycin embonate for use in animal feed, and as the adipate, a more soluble form, for administration by other routes. It has also been used in the protozoal infections cryptosporidiosis and toxoplasmosis. HUMAN EXPOSURE AND TOXICITY: Spiramycin is reported to cause contact dermatitis in occupational settings. A man who worked in a feed factory developed allergic contact dermatitis due to airborne spiramycin. The patient suffered recurrent outbreaks of eczematous lesions on uncovered areas during working periods. Spiramycin is also reported to cause hypersensitivity reactions. Rhinoconjunctivitis and spasmodic cough are reported in a 34 year-old female handling spiramycin powder in a pharmaceutical factory. The symptoms appeared within the first few hours of coming into contact with the drug and continued for several hours after leaving her place of work. One year after starting work in the pharmaceutical industry a 35-year-old non-atopic maintenance engineer developed attacks of sneezing, coughing and breathlessness. Inhalation challenge tests carried out in the hospital with gradually increasing quantities of spiramycin reproduced his symptoms and led to the development of late asthmatic reactions. Additionally, two cases of bronchial asthma due to spiramycin in workers of a pharmaceutical factory were reported. The subjects complained of cough, breathlessness and symptoms of asthma at work when coming into contact with spiramycin's powder. The symptoms cleared when away from work for more than 3 or 4 days. ANIMAL STUDIES: Groups of 2 male and 2 female monkeys (Macaca fascicularis) were given daily intravenous injections of 0, 240,000, 360,000, and 540,000 iu/kg bw/day spiramycin adipate for 5 days. Hypersalivation occurred during injection in all dose groups. Muscle hypotonia and nauseous spasticity occurred in several high dose monkeys and in one given the low dose. No abnormalities of body weights occurred but food consumption was reduced in all treated animals. A slight decrease in hemoglobin, red cell numbers and hematocrit was noted in high dose animals. In a short-term dietary study in which rats were given the equivalent of up to 3900 mg/kg bw for 13 weeks, the only major effects noted were a reduction in neutrophil counts in some mid- and high-dose animals, and the dilatation of the caecum. In another dietary study in the rat, animals were given up to the equivalent of 720 mg/kg bw/day for one year. The only notable effects were reductions in the body weights of females receiving the high doses, and increases in relative liver, kidney, and adrenal weights at high dose levels in animals of both sexes. Hepatic glycogen depletion occurred at all dose levels but not in controls. In mongrel dogs given 500 mg/kg bw/day for up to 56 days, reductions in spermatogenesis and testicular atrophy occurred. Kidney damage was also seen. When beagles were given orally spiramycin at up to the equivalent of 150 mg/kg bw/day for two years, testicular damage was not seen although degenerative changes occurred in other organs. In teratogenicity studies in mice, oral doses of spiramycin of up to 400 mg/kg bw given over days 5-15 of gestation had no effects on the outcome of pregnancy. intravenous doses of up to 84 mg/kg bw/day given on days 6-15 of gestation to rats and day 6-19 to rabbits had no effect on developmental, but oral dose of 200 and 400 mg/kg bw/day in rabbit produced caecal enlargement in mothers. Groups of 20 pregnant rats were treated intravenously on days 6-15 of gestation with doses of 0, 90 000, 180 000, and 270 000 iu/kg bw/day with spiramycin adipate. The highest dose given produced brief (5 minutes) ataxia and tremors immediately after dosing. A slight but significant reduction in fetal weight occurred at the intermediate dose but all values were within historical control ranges. There were no increased incidences of any fetal anomaly noted in this study. In a study where male rats were given doses of 30 mg/kg bw/day for 8 days by an unspecified route, mitotic and meiotic abnormalities in spermatogonia were noted. Negative result were obtained with spiramycin adipate and embonate in a forward-mutation test in mammalian cells in vitro, in an in vitro cytogenic assay, and in the mouse micronucleus test.

The macrolide antibiotics include natural members, prodrugs & semisynthetic derivatives. These drugs are indicated in a variety of infections & are often combined with other drug therapies, thus creating the potential for pharmacokinetic interactions. Macrolides can both inhibit drug metab in the liver by complex formation & inactivation of microsomal drug oxidising enzymes & also interfere with microorganisms of the enteric flora through their antibiotic effects. Over the past 20 yrs, a number of reports have incriminated macrolides as a potential source of clinically severe drug interactions. However, differences have been found between the various macrolides in this regard & not all macrolides are responsible for drug interactions. With the recent advent of many semisynthetic macrolide antibiotics it is now evident that they may be classified into 3 different groups in causing drug interactions. The first group (e.g. troleandomycin, erythromycins) are those prone to forming nitrosoalkanes & the consequent formation of inactive cytochrome P450-metabolite complexes. The second group (e.g. josamycin, flurithromycin, roxithromycin, clarithromycin, miocamycin & midecamycin) form complexes to a lesser extent & rarely produce drug interactions. The last group (e.g. spiramycin, rokitamycin, dirithromycin & azithromycin) do not inactivate cytochrome P450 & are unable to modify the pharmacokinetics of other cmpds. It appears that 2 structural factors are important for a macrolide antibiotic to lead to the induction of cytochrome P450 & the formation in vivo or in vitro of an inhibitory cytochrome P450-iron-nitrosoalkane metabolite complex: the presence in the macrolide molecules of a non-hindered readily accessible N-dimethylamino group & the hydrophobic character of the drug. Troleandomycin ranks first as a potent inhibitor of microsomal liver enzymes, causing a significant decr of the metab of methylprednisolone, theophylline, carbamazepine, phenazone (antipyrine) & triazolam. Troleandomycin can cause ergotism in patients receiving ergot alkaloids & cholestatic jaundice in those taking oral contraceptives. Erythromycin & its different prodrugs appear to be less potent inhibitors of drug metab. Case reports & controlled studies have, however, shown that erythromycins may interact with theophylline, carbamazepine, methylprednisolone, warfarin, cyclosporin, triazolam, midazolam, alfentanil, disopyramide & bromocriptine, decreasing drug clearance. The bioavailability of digoxin appears also to be increased by erythromycin in patients excreting high amounts of reduced digoxin metabolites, probably due to destruction of enteric flora responsible for the formation of these cmpds. These incriminated macrolide antibiotics should not be administered concomitantly with other drugs known to be affected metabolically by them, or at the very least, combined admin should be carried out only with careful patient monitoring.|Reduced plasma concentrations of levodopa have been reported when given with spiramycin.|The authors report the case of a 21 year old woman with a congenital long QT syndrome who had several syncopal attacks at least one of which was caused by torsades de pointes. This sudden complication was attributed to the simultaneous prescription of Spiramycine and Mequitazine over a 48 hour period. These two drugs are not considered to be predisposing factors for torsades de pointes despite the fact that they belong to two families of drugs which can trigger this type of arrhythmia. The withdrawal of this treatment led to the complete regression of the syncopal episodes with a follow-up of two years and a significant shortening of the initial QTc interval which remained, nevertheless, longer than normal. This case underlines the potential risks of drug associations of these two families of drugs, especially in patients with the congenital long QT syndrome.

LD50 Rat oral 3550 mg/kg|LD50 Rat ip 575 mg/kg|LD50 Rat sc 1 g/kg|LD50 Rat iv 170 mg/kg|For more Non-Human Toxicity Values (Complete) data for SPIRAMYCIN (23 total), please visit the HSDB record page.

Spiramycin is produced by Streptomyces ambofaciens from soil of northern France(1).

Spiramycin's production and use as an antibiotic(1) may result in its release to the environment through various waste streams(SRC). Spiramycin has not been approved for use in the United States(2).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a structure estimation method(2), indicates that spiramycin is expected to have high mobility in soil(SRC). However, estimated pKa values of 7.88 and 9.28(3), indicate that this compound will exist almost entirely in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of spiramycin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9X10-35 atm-cu m/mole(SRC), using a fragment constant estimation method(2) and the estimated pKa values(3). Spiramycin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-31 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation of spiramycin was 70% in 28 days digested in poultry manure under aerobic conditions(5) and 95% in 32 days digested by sludge under anaerobic conditions(6) suggesting that biodegradation is an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 140(SRC), determined from a structure estimation method(2), indicates that spiramycin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces of the neutral form is not expected(3) based upon an estimated Henry's Law constant of 9.9X10-31 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Estimated pKa values of 7.88 and 9.28(4) indicate spiramycin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation from water surfaces is not expected to be an important fate process(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound did not hydrolyze at 25 °C in buffer solutions at pH 4 to 9(5). According to a classification scheme(6), an estimated BCF of 8(SRC), from an estimated log Kow of 1.87(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation of spiramycin was 70% in 28 days digested in poultry manure under aerobic conditions(7) and 95% in 32 days, digested by sludge under anaerobic conditions(8) suggesting that biodegradation is an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), spiramycin, which has an estimated vapor pressure of 9.9X10-31 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase spiramycin may be removed from the air by wet and dry deposition(SRC). Spiramycin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Spiramycin exhibited no observable hydrolysis under at 25 °C in buffer solutions at pH 4 to 9(1). Five degradation products of spiramycin were detected in river water sampled from eight locations on the Po River (Italy), three of them were thought to be formed through a direct photolysis process and the other two through indirect photolysis(2).

An estimated BCF of 8 was calculated in fish for spiramycin(SRC), using an estimated log Kow of 1.87(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of spiramycin can be estimated to be 140(SRC). According to a classification scheme(2), this estimated Koc value suggests that spiramycin is expected to have high mobility in soil. Estimated pKa values of spiramycin are 7.88 and 9.28(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

Estimated pKa values of 7.88 and 9.28(1) indicate spiramycin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation form from water and moist soil surfaces is not expected to be an important fate process(SRC). The Henry's Law constant for spiramycin is estimated as 9.0X10-35 atm-cu m/mole(SRC) using a fragment constant estimation method(2). This Henry's Law constant indicates that the neutral form of spiramycin is expected to be essentially nonvolatile from water and moist soil surfaces(3). Spiramycin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-31 mm Hg(SRC), determined from a fragment constant method(2).

SURFACE WATER: Spiramycin was detected in surface water samples collected from the Italian Po river at Chivasso, Mezzano and from the Lambro river at Parco Lambro at 43.80, 9.79 and 74.20 ng/L, respectively; spiramycin was not detected (detection limit 0.05 ng/L) at the other sampling sites of Boscone, Piacenza, Cremona, Casalmaggiore, Pieve Saliceto along the Po river(1). Spiramycin was detected in surface water in the Netherlands; sample locations, dates and concentrations were not reported(2). Spiramycin was detected in four reservoirs that provide drinking water in North China(3).

Occupational exposure to spiramycin may occur through dermal contact with this compound at workplaces where spiramycin is produced or used. Monitoring and use data indicate that the general population is not likely to be exposed to spiramycin unless by direct medical treatment. (SRC)

Urinary excretion of unchanged spiramycin is 10-20% of the amount ingested in humans(1).

Anti-Bacterial Agents; Coccidiostats|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Spiramycin is included in the database.|MEDICATION (VET): Spiramycin is a macrolide antibiotic used for the treatment and control of a number of bacterial and mycoplasmal infections in animals. It is available as a spiramycin embonate for use in animal feed, and as the adipate, a more soluble form, for administration by other routes.|The aim of this study is to evaluate the efficacy of spiramycin in prevention of mother-to-child transmission of Toxoplasma gondii infection. Patients within first trimester of their pregnancy with Toxoplasma IgM positivity (>0.65 index, ELISA, VIDAS) and IgG positivity (>8 IU/ml), who had low IgG avidity (<0.50 index, ELISA, Architet) were considered as having acute toxoplasmosis. These patients who had amniocentesis at the 19th-21st week of pregnancy were examined for the detection of Toxoplasma DNA. Detailed ultrasonographic examinations performed between the 20th and 24th gestational weeks and the mothers and babies were followed for at least one year. ut of 61 patients, 55 (90.2%) had received Spy prophylaxis while 6 (9.8%) cases refused Spy prophylaxis. Toxoplasma PCR test was found to be positive in amniotic fluid of 4 (6.6%) patients obtained by amniocentesis at the 19th-21st week of pregnancy. All four of these patients had refused Spy prophylaxis had positive Toxoplasma PCR in amniotic fluid (p < 0.01). Our results seem to encourage the use of spiramycin in women with toxoplasmosis during pregnancy.|Spiramycin is a macrolide antibacterial that is used similarly to erythromycin in the treatment of susceptible bacterial infections. It has also been used in the protozoal infections cryptosporidiosis and toxoplasmosis.

The most frequent adverse effects are gastrointestinal disturbances. Transient parethesia has been reported during parenteral use.|Spiramycin, a 16-membered lactone ring macrolide, has been in clinical use for the past 15 years with little serious associated toxicity. GI disturbance has usually been mild & no changes in GI motility have been noted either experimentally or in humans, in contrast to other macrolides, such as erythromycin. Allergic reactions have been uncommon & mainly restricted to transient skin eruptions. Although liver injury is a possible complication of most macrolide treatments, no conclusive evidence for spiramycin-induced hepatitis is currently available, and, again in contrast to most other macrolides, the lack of drug interactions with spiramycin has been clearly established in biochemical, pharmacokinetic & clinical studies.|... Allergic drug reactions to macrolides are extremely rare & there is little information in the literature concerning relevant diagnostic tests. ... Twenty-one patients were recently seen for assumed allergies (principally urticaria) to diverse macrolides. Skin tests (prick & intradermal tests) were performed with injectable forms of spiramycin & erythromycin. Seventeen out of 21 patients were provoked under strict hospital surveillance. ... Only 3 patients had a positive provocation test & were thus truly allergic (to spiromycin). They had positive skin tests to both macrolides tested. ... Most hypersensitivity reactions to macrolides are therefore diagnosed with provocation tests.|We recently reported two cases of QT interval prolongation & cardiac arrest in newborns receiving antibiotic therapy with spiramycin, a macrolide agent extensively used for toxoplasmosis prophylaxis. In this study we assessed the effects of this drug on ventricular repolarization & on the potential risk of lethal arrhythmias in 8 newborn infants in whom toxoplasmosis prophylaxis after birth was necessary. Electrocardiograms (ECGs) & echocardiograms were recorded during spiramycin therapy (350,000 i.u./kg/ day) & after its withdrawal. In a control group of 8 healthy newborns matched for age & sex, no differences were found between 2 ECGs analogously recorded. The QT interval corrected for heart rate (QTc) was longer during spiramycin therapy than after drug withdrawal (448 +/- 32 msec vs 412 +/- 10 msec, +9%, p=0.021). QTc dispersion, expressed as the difference between the longest & the shortest value in 12 different leads (QTcmax-min), was also higher during spiramycin therapy (60 +/- 32 msec vs 34 +/- 8 msec, +76%, p=0.021), mainly because of a major lengthening of the longest QTc (QTcmax). QTc & QTc dispersion were markedly increased in the 2 newborns who experienced cardiac arrest after beginning treatment compared with the 6 neonates who had no drug-induced symptoms. During therapy 7 of 8 newborns had a rare abnormality in the thickening of the left ventricular posterior wall similar to that observed in patients with congenital long QT syndrome. This abnormality disappeared after drug withdrawal. Thus antibiotic therapy with spiramycin in the neonatal period may induce QT interval prolongation & incr QT dispersion. When this effect on ventricular repolarization is more marked, it may favor the occurrence of torsades des pointes & lead to cardiac arrest.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)|Agents useful in the treatment or prevention of COCCIDIOSIS in man or animals. (See all compounds classified as Coccidiostats.)

Spiramycin is well absorbed in humans after oral administration. Oral administration of 15-30 mg/kg bw to healthy young male adults resulted in peak plasma levels in 3-4 hours and plasma concentrations of 0.96-1.65 mg/l. After intravenous dosing (7.25 mg/kg b.w.) a large volume of distribution (Vdss 5.6 l/kg) was observed indicating extensive tissue distribution. Biotransformation did not appear to be important. Biliary excretion was the main route of excretion; only 7-20% of an oral dose was excreted in the urine. Spiramycin is known to achieve high tissue:serum concentrations in pulmonary and prostatic tissues, and in skin.|Spiramycin crosses the placenta to the fetus. Concns of the antibiotic in maternal serum, cord blood, & the placenta after a dosage regimen of 2 g/day were 1.19 ug/ml, 0.63 ug/ml, & 2.75 ug/ml, respectively. When the maternal dose was increased to 3 g/day, the levels were 1.69 ug/ml, 0.78 ug/ml, & 6.2 ug/ml, respectively. Based on these results, the cord:maternal serum ratio is approx 0.5. Moreover, at these doses, spiramycin is concentrated in the placenta with levels approx 2-4 times those in the maternal serum. ... Spiramycin is excreted into breast milk. Nursing infants of mothers receiving 1.5 g/day for 3 days had spiramycin serum concns of 20 ug/ml. This concn was bacteriostatic.|/MILK/ Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma & milk after iv, intramuscular & subcutaneous admin. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma & milk were collected post injection. Spiramycin concn in the plasma was determined by a high performance liquid chromatography method, & in the milk by a microbiological method. The mean residence time after iv admin was significantly longer (P<0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concn-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous admin was almost 100% & was bioequivalent for the extravascular routes, but the rates of absorption, the max concns & the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for max concn in the milk. However, the two routes were bio-equivalent for the duration of time the milk concn exceeded the minimal inhibitory concn (MIC) of various pathogens causing infections in the mammary gland.|Plasma protein binding ranges from 10 to 25%. An oral dose of 6 million units produces peak blood concentrations of 3.3 ug/mL after 1.5 to 3 hours; the half life is about 5 to 8 hours. High tissue concentrations are achieved and persist long after the plasma concentration has fallen to low levels.|For more Absorption, Distribution and Excretion (Complete) data for SPIRAMYCIN (13 total), please visit the HSDB record page.

In cattle, the metabolite neospiramycin, the demycarosyl derivative, is formed. Concentrations of neospiramycin in muscle and kidney were marginally higher than those of spiramycin 14-28 days after dosing; in muscle, levels of neospiramycin and spiramycin were approximately equal.|Spiramycin is metabolized in the liver to active metabolites; substantial amounts are excreted in the bile and about 10% in the urine.

An oral dose of 6 million units produces ... /a/ half life is about 5 to 8 hours.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, anaphylaxis, and hemolysis if they occur. 3. replace fluid losses resulting from gastroenteritis with IV crystalloids. 4. Maintain steady urine flow with fluids to alleviate crystalluria from overdoses of sulfonamides, ampicillin, or amoxicillin. /Antibacterial agents/|For more Antidote and Emergency Treatment (Complete) data for SPIRAMYCIN (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ The effects of orally administered spiramycin on the faecal and oral bacterial flora of humans were studied in healthy volunteers. Six subjects were given 1 g spiramycin twice a day for 5 days. Fecal and saliva samples were collected for examination before treatment with the drug, during the treatment, and 7 and 21 days after. There was no evidence of an increased colonization of the oral cavity by enterobacteria, enterococci, staphylococci or fungi as a result of treatment with spiramycin. The mean anaerobe counts of feces were not affected by spiramycin intake; there were no effects on enterobacteria and enterocci counts. Similarly, there were no increases in fungi, staphylococci or Pseudomonas aeruginosa. There was a shift in the numbers of enterobacteria resistant to the effects of high concentrations of spiramycin with counts increasing during treatment. Similarly, increases in Minimum Inhibitory Concentration (MIC) values for anaerobes and enterococci occurred during treatment. These changes were considered by the authors merely to reflect a selective pressure in the treatment period and they concluded that spiramycin had a limited effect on the intestinal flora of healthy volunteers at 2 g per day (approximately 33 mg/kg/day).|/CASE REPORTS/ One year after starting work in the pharmaceutical industry a 35-year-old non-atopic maintenance engineer developed attacks of sneezing, coughing and breathlessness. These occurred at home during the evening and early morning, never at work during the day. His employment involved contact with a wide variety of chemical agents including the macrolide antibiotic spiramycin. Inhalation challenge tests carried out in hospital with gradually increasing quantities of spiramycin reproduced his symptoms and led to the development of late asthmatic reactions, during which the FEV1 fell by 25% and the FEV1/FVC ratio by 15%. No change occurred in the single breath CO transfer factor nor were crepitations heard over the lung fields which remained normal on chest X-ray. The patient showed positive immediate skin prick tests to spiramycin and developed blood eosinophilia during the late asthma attacks. Inhalation of sodium cromoglycate either before, or before and hourly after the provocation challenge for 6 hr, failed to prevent the late asthma, although its onset was further delayed. On leaving the pharmaceutical industry the patient's symptoms improved but did not finally clear until his wife, who had worked in a clerical capacity in the same factory also ceased her employment.|/CASE REPORTS/ A case report of airborne contact dermatitis due to occupational exposure to animal feed antibiotics was presented. A 43 yr old man who had worked for 13 yrs in cattle breeding presented with an 18 month history of erythema, edema, & vesicles on the interdigital spaces of the hands, the face, & both sides of the neck. Part of his duties was to prepare a special drink formulation for suckling & weaning calves for which he mixed a powdered commercially prepared animal feed with water & a variety of antibiotics. His symptoms worsened whenever he prepared this animal feed. He was patch tested with the GIRDCA standard series, a preservatives series, & numerous antibiotics. Positive reactions were detected at 2 & 3 days to oxytetracycline-hydrochloride, tylosin, penicillin, & spiramycin. The dermatitis completely cleared as soon as the patient left his occupation. The authors strongly recommend the testing of animal feed workers with the most commonly used feed additives, even if their dermatitis is not thought to be related to their jobs & even if the clinical features are not suggestive of an occupational cause.|/CASE REPORTS/ The authors report the case of a 21 year old woman with a congenital long QT syndrome who had several syncopal attacks at least one of which was caused by torsades de pointes. This sudden complication was attributed to the simultaneous prescription of Spiramycine and Mequitazine over a 48 hour period. These two drugs are not considered to be predisposing factors for torsades de pointes despite the fact that they belong to two families of drugs which can trigger this type of arrhythmia. The withdrawal of this treatment led to the complete regression of the syncopal episodes with a follow-up of two years and a significant shortening of the initial QTc interval which remained, nevertheless, longer than normal. This case underlines the potential risks of drug associations of these two families of drugs, especially in patients with the congenital long Qt syndrome.|For more Human Toxicity Excerpts (Complete) data for SPIRAMYCIN (12 total), please visit the HSDB record page.

Antibiotic 799

Spiramycin is available in combination preparations with metronidazole in some countries.|Antibiotic consists of three closely related macrolide components, I, II, and III, whose ratio is 2:1:1.

Not commercially available in US.|Spiramycin is not commercially available in the U.S., but is obtainable as an orphan drug through the National Information Center for Orphan Drugs & Rare Diseases.|Spiramycin is a mixture of three macrolide antibiotics containing a sixteen-membered lactone ring, substituted with amino sugars and mycarosyl. The components are designated spiramycin I, II, and III, with spiramycin I being the most important. The antimicrobial spectrum of spiramycin is similar to that of other macrolide antibiotics, but its activity against Treponema is greater than that of erythromycin or oleandomycin.

Veterinary Drug -> ANTIMICROBIAL_AGENT; -> JECFA Functional Classes

Veterinary Drug -> ANTIMICROBIAL_AGENT;