Tiamulin

493.74

493.74

259-580-0

DTXSID2046701

Sticky, translucent yellowish mass

2941906000

92.14000

5.93

1.1±0.1 g/cm3

147-148ºC

563.0±50.0 °C at 760 mmHg

294.3±30.1 °C

1.541

Practically insoluble in water

Protect from direct sunlight. Store at controlled room temperature, 59 deg - 77 °F (15 deg -25 °C).|Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place. Containers which are opened must be carefully resealed and kept upright to prevent leakage. Recommended storage temperature: 2-8 °C.

4.2X10-14 mm Hg at 25 °C (est)

Henry's Law constant = 4.2X10-16 atm-cu m/moleat 25 °C (est)

pKa = 9.51 (est)

Slightly hygroscopic

NONH for all modes of transport

2

AG9552000

Stable under recommended storage conditions.

H413

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.

Tiamulin. Oral dosage form new animal drugs. Conditions of use in swine.|A tolerance of 0.6 part per million is established for 8-alpha-hydroxymutilin (marker compound) in liver (target tissue) of swine.|Tiamulin. New animal drug for use in animal feeds. Conditions of use in swine.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Tiamulin is included on this list.|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Tiamulin hydrogen fumarate is included on this list. /Tiamulin hydrogen fumarate/

H413 (92.68%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]|P273, and P501|Aggregated GHS information provided by 44 companies from 5 notifications to the ECHA C&L Inventory.|H413: May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]

Skin protection: Handle with gloves.|Eye/face protection Face shield and safety glasses: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face respirator with multipurpose combination (US) or type ABEK (EN 14387) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).|Body Protection: Impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

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 breathing vapors, mist or gas. Ensure adequate ventilation. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Soak up with inert absorbent material and dispose of as hazardous waste. 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.|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.

Direct contact with skin or mucous membranes may cause irritation.

A tolerance of 0.6 part per million is established for 8-alpha-hydroxymutilin (marker compound) in liver (target tissue) of swine.

Tiamulin was detected in 10% of samples from 90 waste water treatment plants at 20-44.3 ng/L; samples were collected throughout Europe (1 from Slovenia; 2 each from Cyprus, Germany, Greece, Hungary, Ireland, Italy, Portugal; 3 from Lithuania and Spain; 5 from France and Switzerland; 6 from Austria and Finland; 7 from the Czech Republic, 11 from the Netherlands and Sweden; 18 from Belgium) in 2010(1). Tiamulin was detected at 0.09 ng/L in the influent samples collected from a wastewater treatment plant located in Beijing, China(2).

SEDIMENT: Tiamulin was detected in sediment samples from the Bay of Cadiz, Spain in samples collected March and September of 2011; all concentrations were 0.10 mg/kg or less; samples were from 6 locations (Chiclana de la Frontera, Puerto Real, Cadiz, two locations at El Puerto di Santa Maria and Rota)(1).

The maximum concentration of tiamulin found in manure samples was 43 ug/kg(1).

IDENTIFICATION AND USE: Tiamulin, when administered in the drinking water for five consecutive days, is an effective antibiotic for the treatment of swine dysentery associated with Brachyspira (formerly Serpulina or Treponema) and for treatment of swine pneumonia due to Actinobacillus pleuropneumoniae. As a feed additive, it is used to cause increased weight gain in swine. HUMAN EXPOSURE AND TOXICITY: Topical administration of a 0.05% formulation of tiamulin did not cause skin irritation or sensitization. Another study was carried out in 6 healthy male human volunteers. Three volunteers were given 5 oral doses progressing from 0.125 to 7.2 mg/kg bw with 72 hours between each dose. The remaining volunteers were given a single oral dose in the range of 8.2 to 10.7 mg/kg bw tiamulin. There was no substance-related changes in blood pressure, serum chemistry or electrocardiograms. ANIMAL STUDIES: Overdoses of tiamulin have produced transitory salivation, vomiting and an apparent calming effect on the pig. In a subchronic study, rats were fed diets containing 0.5 or 30 mg tiamulin/kg bw/day for 26 weeks. Further groups of rats received 180 mg/kg bw/day for 10 weeks, followed by 270 mg/kg bw/day for 16 weeks; one group was necropsied at the end of treatment, the remaining rats were maintained on untreated control diets for a further 4 or 8 weeks. There were increases in serum cholesterol and in water intake in the 180 mg/kg bw group. When the dose was increased to 270 mg/kg bw/day, the effects included increased serum alkaline phosphatase, alanine phosphatase, alanine aminotransferase and aspartate aminotransferase. Abdominal distension, dense feces and increased urine specific gravity were also observed. Absolute and relative liver weights were increased in both sexes and fatty infiltration of the liver was observed on histopathological examination. In a chronic study, dogs were given daily oral doses of 0, 3, 10 or 30 mg/kg bw/day of tiamulin for 54 weeks. In the groups given 10 and 30 mg/kg bw/day, occasional emesis was observed, serum potassium concentrations were decreased and electrocardiograms showed prolongation of the QT interval. Serum lactate dehydrogenase (LDH) was significantly increased; there was no increase in the cardiac-related isoenzyme LDH1. Rats were fed diets containing tiamulin at concentrations designed to provide intakes of 0, 2, 8 or 32 mg/kg bw/day of tiamulin for 30 months. There was no significant dose-related trend in the incidence of any tumor type. In another study, mice were fed diets containing the equivalent of 0, 1, 6 or 48 mg/kg bw/day of tiamulin for up to 123 weeks. There was no significant dose-related trend in the incidence of any tumor type. Pregnant female rats were given daily oral doses of 0, 30, 100 or 300 mg/kg bw/day from days 6 to 15 of gestation. At 300 mg/kg bw/day there were minor signs of maternal toxicity. At this dose level, the mean fetal weight was reduced and there was an increased incidence of retarded skeletal development. There was no evidence of teratogenicity. Pregnant female rabbits were given daily oral doses of 0, 30, 55 or 100 mg/kg bw/day from days 6 to 18 of gestation. Doses of 55 mg/kg bw/day and above caused the deaths of some dams and maternal body weight gain was reduced. Litter size and fetal weights were reduced at 55 mg/kg bw/day and above. There was no evidence of teratogenicity at any dose level. Several reproductive studies were performed in pigs. Breeding sows were fed a diet containing 200 mg/kg feed from days 84 to 92 of gestation, another group was maintained on a diet containing 16 mg/kg bw/day from 2 days after mating for 6 weeks, and further groups were given tiamulin in the drinking water at a dose of 8.8 mg/kg bw/day for various periods during gestation and in some cases up to weaning of the offspring. There were no adverse effects on health of the sows, pregnancy, parturition, letter size, growth and survival of the piglets, estrus cycle or subsequent breeding performance. When given to breeding boars, at a diet containing 16 mg/kg bw/day for 14 days, there were no effects on health status, libido or semen quality. Tiamulin did not induce gene mutations in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 or TA1538. An in vitro assay for gene mutation at the HPRT locus of V79 Chinese hamster cells also gave negative results. In an in vivo micronucleus test in mice tiamulin had no effect on the frequency of micronucleated polychromatic erythrocytes.

The characteristics of the toxic interaction between monensin & tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg & tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 & 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined admin, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect & vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous admin of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium & vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the admin of 50 mg/kg monensin alone.|Studies were carried out to investigate the effects of monensin & tiamulin, & the simultaneous admin of both compounds on microsomal enzymes in rats. In Phase I of the experiments the effects of monensin & tiamulin were studied separately (monensin 10, 30, & 50 mg/kg or tiamulin 40, 120, & 200 mg/kg body weight, respectively), while in Phase II the two compounds were administered simultaneously (monesin 10 mg/kg & tiamulin 40 mg/kg b.w., respectively). When monensin was administered by itself, it exerted no significant effect on microsomal liver enzymes. In a few cases, slight inhibition of certain enzyme activities was seen. Tiamulin provoked a dose-dependent hepatic enzyme induction. The combined admin of monensin & tiamulin at low doses (10 & 40 mg/kg, respectively) resulted in marked elevation of P450-related enzyme activities. The enzyme induction was more pronounced in females than in males. The results suggest that the simultaneous admin of tiamulin may influence the biotransformation of monensin, possibly increasing the amount of reactive metabolite(s) of the ionophore antibiotic.|Tiamulin is an antibiotic frequently used in veterinary medicine. The drug has been shown to produce clinically important interactions with other compounds that are administered simultaneously. An NIH/3T3 cell line, stably expressing human cytochrome P450 (EC 1.14.14.1) cDNA (CYP3A4), was used to study the effect of tiamulin on CYP3A4 activity. The 6 beta-hydroxylation activity of testosterone, which is increased in CYP3A4-expressing cells compared to vector-transfected cells, showed reduced activity after incubation with 1 microM tiamulin and was completely reduced to background level after incubation with 2, 5 and 10 microM tiamulin. The CYP3A4-expressing cell line was used in combination with a shuttle vector containing the bacterial lacZ' gene to study the effect of tiamulin on CYP3A4-mediated mutagenicity of aflatoxin B1. The mutation frequency of aflatoxin B1 could be completely inhibited by tiamulin in CYP3A4-expressing cells, but no effect was observed on the mutation frequency of the direct mutagen ethylmethanesulphonate. Western blotting of homogenates of the CYP3A4-expressing cell line showed stabilization of CYP3A4 protein after incubation with tiamulin, supporting the hypothesis that the mechanism of inhibition is by binding of tiamulin to the cytochrome.|In poultry, tiamulin interferes with monensin and salinomycin metabolism, and if the drugs are fed together, they become toxic.|For more Interactions (Complete) data for TIAMULIN (10 total), please visit the HSDB record page.

LD50 Rat oral 2230 mg/kg|LD50 Rat sc 4380 mg/kg|LD50 Rat iv 20 mg/kg|LD50 Mouse oral 710 mg/kg|For more Non-Human Toxicity Values (Complete) data for TIAMULIN (15 total), please visit the HSDB record page.

Tiamulin's production and use as an antibiotic(1), and as a growth enhancer in livestock and poultry(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 36,000(SRC), determined from a structure estimation method(2), indicates that tiamulin is expected to be immobile in soil(SRC). The estimated pKa of tiamulin is 9.51(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). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Tiamulin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Tiamulin had a biodegradation half-life of 16 days in soil based on a 120 day aerobic biodegradation soil test(5), however, under anaerobic conditions tiamulin was not biodegraded(6).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 36,000(SRC), determined from a structure estimation method(2), indicates that tiamulin is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 9.51(3) indicates tiamulin will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization of the cation form from water surfaces is not expected to be an important fate process(SRC). Tiamulin has estimated hydrolysis half-lives of 180 and 18 days at pH values of 7 and 8, respectively(2). According to a classification scheme(4), an estimated BCF of 640(SRC), from an estimated log Kow of 4.75(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Based on biodegradation studies in soil, tiamulin may biodegrade under aerobic conditions in water(5).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tiamulin, which has an estimated vapor pressure of 4.2X10-14 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 tiamulin may be removed from the air by wet and dry deposition(SRC). Tiamulin contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

A base-catalyzed second-order hydrolysis rate constant of 0.44 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 180 and 18 days at pH values of 7 and 8, respectively(1). Tiamulin contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 640 was calculated in fish for tiamulin(SRC), using an estimated log Kow of 4.75(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of tiamulin can be estimated to be 36,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that tiamulin is expected to be immobile in soil. The estimated pKa of tiamulin is 9.51(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). Tiamulin in swine waste water had log Kd values of 1.54-1.58, 5-10% of tiamulin was partitioned to the suspended solids phase(5).

An estimated pKa of 9.51(1) indicates tiamulin 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 the neutral species of tiamulin is estimated as 4.2X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(2). This Henry's Law constant indicates that the neutral form of tiamulin is expected to be essentially nonvolatile from water and moist soil surfaces(3). Tiamulin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.2X10-14 mm Hg(SRC), determined from a fragment constant method(2).

Tiamulin residues were detected in multiflora honey samples collected from veterinarian-treated beehives(1).

Occupational exposure to tiamulin may occur through inhalation of dust and dermal contact with this compound at workplaces where tiamulin is produced or used. Monitoring and use data indicate that the general population is not likely to be exposed to tiamulin. (SRC)

Anti-Bacterial Agents|MEDICATION (VET): Denagard (tiamulin), when administered in the drinking water for five consecutive days, is an effective antibiotic for the treatment of swine dysentery associated with Brachyspira (formerly Serpulina or Treponema) hyodysenteriae susceptible to tiamulin at a dose level of 3.5 mg tiamulin hydrogen fumarate per pound of body weight daily and for treatment of swine pneumonia due to Actinobacillus pleuropneumoniae susceptible to tiamulin when given at 10.5 mg tiamulin hydrogen fumarate per pound of body weight daily. /Included in US product label/|MEDICATION (VET): Tiamulin is a diterpenic veterinary drug widely used in swine for the control of infectious diseases, including swine dysentery & enzootic pneumonia.|MEDICATION (VET): In veterinary medicine, tiamulin is used for treatment and prophylaxis of dysentery, pneumonia and mycoplasmal infections in pigs and poultry.

For use in animals only - Not for human use.|Swine being treated with Denagard (tiamulin) should not have access to feeds containing polyether ionophores (e.g., monensin, lasalocid, narasin, salinomycin and semduramicin) as adverse reactions may occur.|Adverse effects occurring with this drug at usual doses are considered unlikely. Rarely, redness of the skin, primarily over the ham and underline, has been observed. It is recommended to discontinue the medication, provide clean drinking water, and hose down the area or move affected animals to clean pens.|In poultry, tiamulin interferes with monensin and salinomycin metabolism, and if the drugs are fed together, they become toxic.

Different groups of antibiotics bind to the peptidyl transferase center (PTC) in the large subunit of the bacterial ribosome. Resistance to these groups of antibiotics has often been linked with mutations or methylations of the 23S rRNA. In recent years, there has been a rise in the number of studies where mutations have been found in the ribosomal protein L3 in bacterial strains resistant to PTC-targeting antibiotics but there is often no evidence that these mutations actually confer antibiotic resistance. In this study, a plasmid exchange system was used to replace plasmid-carried wild-type genes with mutated L3 genes in a chromosomal L3 deletion strain. In this way, the essential L3 gene is available for the bacteria while allowing replacement of the wild type with mutated L3 genes. This enables investigation of the effect of single mutations in Escherichia coli without a wild-type L3 background. Ten plasmid-carried mutated L3 genes were constructed, and their effect on growth and antibiotic susceptibility was investigated. Additionally, computational modeling of the impact of L3 mutations in E. coli was used to assess changes in 50S structure and antibiotic binding. All mutations are placed in the loops of L3 near the PTC. Growth data show that 9 of the 10 mutations were well accepted in E. coli, although some of them came with a fitness cost. Only one of the mutants exhibited reduced susceptibility to linezolid, while five exhibited reduced susceptibility to tiamulin.

It is readily absorbed from the gut and can be found in the blood within 30 minutes after dosing.|Tiamulin is well absorbed orally by swine. Approximately 85% of a dose is absorbed and peak levels occur between 2-4 hours after a single oral dose. Tiamulin is apparently well distributed, with highest levels found in the lungs.|In pigs (2 animals per sex and group), following oral administration of 5 mg (14)C-tiamulin base/kg bw/day for 10 consecutive days, approximately 35% of the dose was eliminated in urine and 65% in feces. The total residue concentrations in liver, kidney, muscle and fat were 21,880, 600, 720 and 720 ug equivalents/kg, respectively, 10 days after dosing and 480, 220, 430, 910 ug equivalents/kg after 25 days.

In laying hens, broilers and turkeys (6 animals per group) orally dosed with 10 mg (3)H-tiamulin hydrogen fumarate/kg bw/day for 5 consecutive days, over 15 metabolites were detected in tissue extracts but most of the residue was accounted for by 4 metabolites. No individual metabolite represented more than 30% of the total residue in poultry tissues.|In the liver of pigs orally treated with tiamulin, the percentage of the metabolites that can be hydrolyzed to 8-alpha-hydroxymutilin (ie marker residue) to total residues was 3.5, 3.6 and 5.7% at 4, 24 and 96 hours after treatment, respectively.|In pigs (4 animals per sex and group) given ad libitum access to feed containing tiamulin at a concentration of 39 mg/kg for 10 consecutive days, the average concentrations of metabolites in liver that could be hydrolyzed to form 8-alpha-hydroxymutilin, as detected by gas chromatography with electrochemical detection, were 447 and 247 ug equivalent/kg at 2 and 12 hours after dosing, respectively. In animals does for 18 consecutive days, the average concentrations of 8-alpha-hydroxymutilin in liver were 184, 256, 214 and 175 ug equivalents/kg at 12, 16, 20 and 24 hours after dosing, respectively.|In pigs orally dosed with (3)H-tiamulin, 6-desmethyltiamulin accounted for less than 1% of the total residue in bile and urine samples and had 67% of the antimicrobiological activity of tiamulin when tested by agar plate diffusion. Four other metabolites were found to have antimicrobiological activities relative to tiamulin of between 0.7 and 3.3% and all other metabolites had relative activities of less than 0.3%.|Tiamulin is extensively metabolized to over 20 metabolites, some having antibacterial activity. Approximately 30% of these metabolites are excreted in the urine with the remainder excreted in the feces.

The mutation frequency of aflatoxin B1 could be completely inhibited by tiamulin in CYP3A4-expressing cells, but no effect was observed on the mutation frequency of the direct mutagen ethylmethanesulphonate. Western blotting of homogenates of the CYP3A4-expressing cell line showed stabilization of CYP3A4 protein after incubation with tiamulin, supporting the hypothesis that the mechanism of inhibition is by binding of tiamulin to the cytochrome.|Tiamulin is a semisynthetic diterpene antibiotic frequently used in farm animals. The drug has been shown to produce clinically important--often lethal--interactions with other compounds. It has been suggested that this is caused by a selective inhibition of oxidative drug metabolism via the formation of a cytochrome P-450 metabolic intermediate complex. In the present study, rats were treated orally for 6 days with tiamulin at two different doses: 40 & 226 mg/kg of body weight. For comparison, another group received 300 mg of triacetyloleandomycin (TAO) per kg, which is equivalent to the 226-mg/kg tiamulin group. Subsequently, microsomal P-450 contents, P-450 enzyme activities, metabolic intermediate complex spectra, & P-450 apoprotein concentrations were assessed. In addition, effects on individual microsomal P-450 activities were studied in control microsomes at different tiamulin & substrate concentrations. In the rats treated with tiamulin, a dose-dependent complex formation as evidenced by its absorption spectrum & an increase in cytochrome P-4503A1/2 contents as assessed by Western blotting (immunoblotting) were found. The effects were comparable to those of TAO. Tiamulin induced microsomal P-450 content, testosterone 6 beta-hydroxylation rate, erythromycin N-demethylation rate, & the ethoxyresorufin O-deethylation activity. Other activities were not affected or decreased. When tiamulin was added to microsomes of control rats, the testosterone 6 beta-hydroxylation rate & the erythromycin N-demethylation were strongly inhibited. It is concluded that tiamulin is a potent & selective inducer-inhibitor of cytochrome P-450. Though not belonging to the macrolides, the compound produces an effect on P-450 similar to those of TAO & related compounds.

/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 TIAMULIN (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ A study was carried out in 6 healthy male human volunteers. Three volunteers were given 5 oral doses progressing from 0.125 to 7.2 mg/kg bw with 72 hours between each dose. The remaining volunteers were given a single oral dose in the range of 8.2 to 10.7 mg/kg bw tiamulin. There was no substance-related changes in blood pressure, serum chemistry or electrocardiograms.|/HUMAN EXPOSURE STUDIES/ In a patch study in humans, topical administration of a 0.05% formulation did not cause skin irritation or sensitization.

Tiamulin Soluble Powder: 45% in 2.28 ox packets (29.1 g tiamulin per packet); Denagard Liquid Concentrate, TiaGard; (OTC).|Tiamulin Solution: 12.3% tiamulin hydrogen fumarate in an aqueous base in 32 oz bottles; Denagard Liquid Concentrate, TiaGard; (OTC).|Tiamulin Medicated Premix: 10 g/1 lb in 35 lb bags; Denagard 10; (OTC).

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