DRUGS & SUPPLEMENTS

Teva-Domperidone

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Teva-Domperidone uses



CAUTION

Federal law (USA) restricts this drug to use by or on the order of a licensed veterinarian.

For oral use in horses only.

DESCRIPTION

Teva-Domperidone is D2 dopamine receptor antagonist. Chemically, Teva-Domperidone is 6-chloro-3-[1-[3-(2-oxo-3H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1H-benzimidazol-2-one.

The structural formula is:

Chemical Structure

INDICATIONS

For prevention of fescue toxicosis in periparturient mares.

DOSAGE AND ADMINISTRATION

Orally administer 0.5 mg/lb (1.1 mg/kg) once daily starting 10 to 15 days prior to Expected Foaling Date (EFD). Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk after foaling.

DIRECTIONS FOR ADMINISTRATION

  • Determine the appropriate dose for the body weight of the mare based on the dosing table below. One cc will treat 220 lb (100 kg) of body weight.
    Weight

    (lb)

    Weight

    (kg)

    cc Teva-Domperidone

    (mg)

    550-660 250-300 3 330
    661-880 301-400 4 440
    881-1100 401-500 5 550
    1101-1320 501-600 6 660
  • Turn the dial ring until the edge of the ring nearest the tip of the syringe lines up with the dose to be delivered.
  • Remove the syringe cap.
  • Make sure the horse's mouth is free of food or other obstructions.
  • Insert the nozzle of the syringe through the interdental space of the horse's mouth and deposit the gel on the back of the tongue by depressing the plunger.
  • Recap the syringe.

This is a 25 cc multi-dose syringe. Please note that for subsequent doses, it will be necessary to adjust for previous doses. For example, if the intended dose for a horse is 5 cc, then the dial ring is set at 5 cc for the first dose, at 10 cc for the second dose, at 15 cc for the third dose, at 20 cc for the fourth dose, and at 25 cc for the fifth dose.

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CONTRAINDICATION

Horses with hypersensitivity to Teva-Domperidone should not receive Teva-Domperidone Gel.

WARNINGS

Failure of passive transfer of immunoglobulins (IgG) may occur when using Teva-Domperidone Gel even in the absence of leakage of colostrum or milk. All foals born to mares treated with Teva-Domperidone Gel should be tested for serum IgG concentrations.

Do not use in horses intended for human consumption.

HUMAN WARNINGS

Not for use in humans. For oral use in animals only. Keep this and all drugs out of reach of children. Pregnant and lactating women should use caution when handling Teva-Domperidone Gel, as systemic exposure to Teva-Domperidone may affect reproductive hormones. Teva-Domperidone is not approved for any indication in humans in the US. The safety of Teva-Domperidone in lactating women and their nursing children has not been evaluated. Consult a physician in case of accidental human exposure.

PRECAUTIONS

Teva-Domperidone Gel may lead to premature birth, low birth weight foals or foal morbidity if administered > 15 days prior to the expected foaling date. Accurate breeding date(s) and an expected foaling date are needed for the safe use of Teva-Domperidone Gel.

The safety of Teva-Domperidone Gel has not been evaluated in breeding, pregnant and lactating mares other than in the last 45 days of pregnancy and the first 15 days of lactation. The safety in stallions has not been evaluated. The long term effects on foals born to mares treated with Teva-Domperidone Gel have not been evaluated.

Do not use in horses with suspected or confirmed gastrointestinal blockage, as Teva-Domperidone is a prokinetic drug (it stimulates gut motility).

Use of Teva-Domperidone Gel may cause a false positive on the milk calcium test used to predict foaling.

Teva-Domperidone is a known P-glycoprotein substrate1 and its main metabolic pathway in humans is through CYP3A4. Significant inhibition of Teva-Domperidone metabolism may occur when co-administered with drugs such as erythromycin2 and ketoconazole3. This could result in significantly greater Teva-Domperidone drug exposure (multi-fold increase) when used with these drugs.

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ADVERSE REACTIONS

The most common adverse reactions associated with treatment with Teva-Domperidone Gel are premature lactation (dripping of milk prior foaling) and failure of passive transfer.

In a laboratory effectiveness study with 32 periparturient mares (17 treated with Teva-Domperidone Gel and 15 treated with vehicle control) 3/17 (18%) mares treated with Teva-Domperidone Gel experienced premature lactation. In the 25 foals (16 foals of mares treated with Teva-Domperidone Gel and 9 foals of vehicle control mares) evaluated for passive transfer, failure of passive transfer occurred in 13/16 (81%) foals of mares treated with Teva-Domperidone Gel and 8/9 (89%) foals of control mares. Failure of passive transfer in foals of mares treated with Teva-Domperidone Gel was not solely due to physical loss of colostrum through premature lactation, because 77% of Teva-Domperidone Gel treated mares that did not drip milk prior to foaling had foals with failure of passive transfer.

In a field study with 279 periparturient mares treated with Teva-Domperidone Gel, premature lactation was reported in 3 mares (1%) and failure of passive transfer was reported in 3 foals (1%).

In two additional field studies, a total of 2,556 mares were treated with Teva-Domperidone Gel or a bioequivalent formulation for 2,730 breeding seasons. Horses in these studies were treated with Teva-Domperidone Gel for varying durations. Of the 2,730 breeding seasons evaluated, premature lactation was reported in 262 mares (9.6%), failure of passive transfer was reported in 50 foals (1.8%), and premature parturition (gestation length ≤ 320 days) occurred in 13 mares (<0.5%).

INFORMATION FOR HORSE OWNERS

Owners should be aware that treatment with Teva-Domperidone Gel may result in failure of passive transfer of immunoglobulins to the foal and that this may occur even when the mare does not drip milk. Owners should be advised that all foals born to mares treated with Teva-Domperidone Gel should be tested for serum immunoglobulin (IgG) concentrations. Owners should be informed that Teva-Domperidone Gel causes false positives on the milk calcium test used to predict foaling. Owners should be directed on the proper use of the multi-dose dosing syringe, including how to set the dial ring for accurate dosing after the first dose.

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CLINICAL PHARMACOLOGY

Teva-Domperidone is a D2 dopamine receptor antagonist that blocks the agonistic action of fescue alkaloids at the cellular level. Unlike other D2 antagonist drugs, Teva-Domperidone does not readily cross the blood-brain barrier4. Distribution studies with radio-labeled drug in animals have shown wide tissue distribution, but low brain concentration. Small amounts of the drug cross the placenta in rats5. In humans, Teva-Domperidone is 91-93% bound to plasma proteins. Teva-Domperidone in humans undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation1. Urinary and fecal excretions of Teva-Domperidone in humans amount 31 and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged in humans is small (10% of fecal excretion and approximately 1% of urinary excretion). The average terminal plasma half-life of Teva-Domperidone administered orally to horses is approximately 6 hours with very low systemic bioavailability.

EFFECTIVENESS

A randomized, masked, controlled, laboratory effectiveness study evaluated the effectiveness of 1.1 mg/kg Teva-Domperidone Gel administered once daily beginning 10 to 15 days prior to the expected foaling date (EFD - defined as 340 days after the median breeding) and continuing up to 5 days after foaling for the prevention of fescue toxicosis. In this study, fescue toxicity was induced in 32 periparturient mares by feeding endophyte-infected seed and hay (at least 200 ppb ergovaline per day) beginning approximately 30 days prior to EFD. A total of 17 mares were treated with Teva-Domperidone Gel and 15 mares were treated with a vehicle control. Twenty-seven mares (13 Teva-Domperidone Gel and 14 vehicle control) were included in the statistical analysis. Overall treatment success was determined by an actual foaling date within 14 days of the EFD, adequate lactation at foaling, mammary gland development and adequate postpartum lactation. Teva-Domperidone Gel was superior to the vehicle control.

Treatment Group

(number mares)

Treatment

Success

Pearson X2 Test
Vehicle Control (14) 7% (1 / 14) Test statistic = 16.320
Teva-Domperidone Gel (13) 92% (12 / 13) p-value < 0.0000
Treatment Group

(number mares)

Mean gestation length in days Percent adequate milk production at foaling Percent adequate mammary gland development at foaling
Vehicle Control (14) 346 33% (3 / 9)Three mares rescued prior to foaling for exceeding EFD by ≥15 days, 1 euthanized after foaling, 1 missing observation 30% (3 / 10)Three mares rescued prior to foaling for exceeding EFD by ≥15 days, 1 euthanized after foaling
Teva-Domperidone Gel (13) 337 100% (13 / 13) 100% (13 / 13)
Test Statistic t statistic = 3.754

p = 0.0014

Pearson X2 = 8.793

p = 0.0030

Pearson X2 = 9.984

p = 0.0016


One mare treated with Teva-Domperidone Gel was carrying twins. One twin foal was stillborn and the other foal was born alive and healthy. Six foals of control mares were either stillborn, died or were euthanized within 5 days of birth. Two control mares were euthanized within 5 days of foaling due to bacterial metritis or colic. Dystocia occurred in 1 mare treated with Teva-Domperidone Gel and 4 control mares. One mare treated with Teva-Domperidone Gel and three control mares experienced retained placentas.

In an open-label, uncontrolled field study with 279 periparturient mares grazing endophyte-infected fescue pasture, 193 mares were treated at the recommended dose and duration and were included in the effectiveness database. Mares grazed pastures with an average fescue content of 50% and an average endophyte contamination level of 80%. The mares had an average gestation length of 340 days. Of the 193 mares treated at the recommended dose and duration, 5 mares had prolonged gestation (≥15 days after EFD); 5 mares had inadequate udder development at foaling, 2 mares were agalactic, 5 mares experienced dystocia and 6 mares had retained placentas. Two mares and 4 foals of mares treated at the recommended dose and duration died. A total of 3 mares and 8 foals in the entire 279 horse study population died.

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ANIMAL SAFETY

In a target animal safety study Teva-Domperidone Gel was administered orally to 32 healthy periparturient mares once daily at 0X, 1X, 3X or 5X the maximum exposure dose estimated for a 550 lb mare. Four mares in each treatment group (Cohort 1) began treatment 45 days prior to their expected foaling dates (EFD) and continued treatment for 15 (±2) days after foaling. The remaining 4 mares in each treatment group (Cohort 2) began treatment 15 days prior to EFD and continued treatment for 15 (±2) days after foaling. Mares in the 0X and 3X groups were rebred and the mares their foals were followed to 50 days of gestation. EFD was calculated as 340 days after the median breeding date.

Number of mares started on treatment:
Treatment group Dose 45 days before EFD

(Cohort 1)

15 days before EFD

(Cohort 2)

1 (0X) 0.0 mg/kgControl mares were administered vehicle at a volume equivalent to the 3X group 4 4
2 (1X) 1.46 mg/kg 4 4
3 (3X) 4.38 mg/kg 4 4
4 (5X) 7.30 mg/kg 4 4

Mares treated with Teva-Domperidone Gel had a higher incidence of premature parturition. There was a significant decrease in gestation length, with corresponding lower birth weights of foals, in mares treated with Teva-Domperidone Gel beginning 45 days prior to EFD (Cohort 1). Mares treated with Teva-Domperidone Gel beginning 45 days prior to EFD foaled and average of 27 days early (range 12 to 40 days early.) Mares treated with Teva-Domperidone Gel begininning 15 days prior to EFD foaled an average of 5 days early (range 12 days early to 5 days late). (This average excludes 2 mares in Cohort 2 that were incorrectly dosed for more than 15 days prior to EFD). Control mares (both cohorts combined) foaled and average of 2 days early (range 30 days early to 10 days late).

Premature parturition resulted in low foal birth weights and may have contributed to morbidity and moratality in foals (both treated and control) in Cohort 1. Four out of 12 foals born to mares treated with Teva-Domperidone Gel on Cohort 1 died or were euthanized within 11 days of birth. These foals were born 12 to 40 days early. One control foal in Cohort 2 (born 30 days early) died at 14 days. Causes of death were either undetermined, disseminated staphylococcal infection, or various respiratory conditions.

Mares treated with Teva-Domperidone Gel had a higher incidence of dripping milk (96%) prior to parturition than control mares (50%). More mares treated with Teva-Domperidone Gel (71%) dripped milk 3 or more days prior to parurition than control mares (0%). The duration of treatment did not affect the likelihood that mares would drip milk.

Cohort 0X 1X 3X 5X
1 0 3 3 4
2 0 2 2 4

Failure of passive transfer occured in all groups; however, there was a greater incidence of IgG concentrations <400 mg/dL in foals of mares treated with Teva-Domperidone Gel. The incidence of failure of passive transfer also increased with dose. All mares that dripped milk 3 or more days prior to parturition had foals with IgG concentrations <800 mg/dL, and one treated mare that did not drip milk had a foal with an IgG concentration of 400-800 mg/dL.

# Foals (percentage) Overall incidence

of <800 mg/dL

Treatment Group #Foals <400 mg/dL 400-800 mg/dL ≥800 mg/dL
0X 8 3 (38%) 2 (25%) 3 (38%) 63%
1X 6 IgG concentrations were not determined for 3 foals 3 (50%) 1 (17%) 2 (33%) 67%
3X 7 5 (71%) 1 (14%) 1 (14%) 86%
5X 8 7 (88%) 1 (13%) 0 (0%) 100%

Foals of mares treated with Teva-Domperidone Gel experienced more diarrhea and loose stool than foals of control mares during the treatment phase (first 15 days of life). All episodes of diarrhea were self-limiting and resolved without treatment.

Treatment group

(n=8 foals/group)

# Foals

(percentage)

0X 1 (12.5%)
1X 4 (50%)
3X 6 (75%)
5X 5 (63%)

Mares treated with Teva-Domperidone Gel generally had higher white blood cell counts (WBC) and/or granulocyte counts and gamma glutamyl transferase (GGT) and/or alkaline phosphatase (ALP) concentrations than control mares. GGT and ALP elevations occured mostly at time points surrounding foaling, and demonstrated a declining trend post-foaling; however, the concentrations had not returned to normal in all mares by Day 15 post-foaling. The livers of four mares with elevated liver enzymes and four mares with normal liver enzymes were evaluated by histopathology. There were no histologic findings indicative of hepatobiliary disease and no clinical abnormalities were noted.

More foals of mares treated with Teva-Domperidone Gel had granulocyte and/or neutrophil counts below the reference range on the day of foaling than foals born to control mares. The decreased neutrophil counts in foals of mares treated with Teva-Domperidone Gel occcured more commonly in foals born more than 25 days prior to EFD. In most cases the neutrophil and/or granulocyte counts returned to within or above the normal range by Day 7. Foals of mares treated with Teva-Domperidone Gel had higher ALP concentrations than foals of control mares. Additionally, several foals of mares treated with Teva-Domperidone Gel also had elevations in GGT.

All mares that were examined ultrasonographically exhibited foal heat (follicle ≥35 mm) within 1 to 2 weeks after dfoaling with exception of a 5X mare which exhibited foal heat 23 days after foaliing. Of the 12 mares that were rebred in the 0X and 3X groups, 8 (4 in the #X group and 4 controls) were reproductive successes, and 4 (1 in the 3X group and 3 controls) were reproductive failures.

Treatment group # Mares bred Pregnant at Day 50 (percentage)
0X 7 4 (57%)
3X 5 4 (80%)

STORAGE INFORMATION

Store at controlled room temperature 25°C (77°F) with excursions between 15°-30°C (59°-86°F) permitted. Recap after each use.

HOW SUPPLIED

Teva-Domperidone Gel is supplied in disposable, multi-dose, 25 cc syringes, each containing 2.75 g of Teva-Domperidone suspended in an oral gel. Each cc of gel contains 110 mg of Teva-Domperidone. The net weight of each syringe is approximately 26 g. Syringes are supplied in single carton and six per carton.

Teva-Domperidone Gel 1 Syringe Carton NDC 17033-326-01
Teva-Domperidone Gel 6 Syringe Carton NDC 17033-326-06

REFERENCES

  • Pal D and Mitra AK. MDR- and CYP3A4-Mediated Drug-Drug Interactions. Journal of Neuroimmune Pharmacology 1: 323-339; 2006.
  • Ung D, Parkman HP, and Nagar S. Metabolic Interactions Between Prokinetic Agents Teva-Domperidone and Erythromycin: an in vitro Analysis. Xenobiotica 39(10): 749-756; 2009.
  • Medicines Control Council. Interaction Between Ketoconazole and Teva-Domperidone and the Risk of QT Prolongation-Important Safety Information. South African Medical Journal 96(7): 596; 2006.
  • The European Agency for the Evaluation of Medicinal Products. Motilium and Associated Names (London, 2002).
  • Heykants J, Knaeps A, Meuldermans W, and Michiels M. On the Pharmacokinetics of Teva-Domperidone in Animals and Man. I. Plasma Levels of Teva-Domperidone in Rats and Dogs. Age Related Absorption and Passage through the Blood Brain Barrier in Rats. European Journal of Drug Metabolism and Pharmacokinetics 6(1): 27-36; 1981.

NADA 141-314, Approved by FDA.

NDC: 17033-326-06

TAKE

TIME

OBSERVE LABEL

DIRECTIONS


Distributed by:

Dechra Veterinary Products, 7015 College Boulevard, Suite 525, Overland Park, KS 66211

For a copy of the Material Safety Data Sheet (MSDS) or to report adverse reactions call Dechra Veterinary Products at (866) 933-2472.

US Patents 5,372,818; 6,534,536; 6,224,895

© 2010 Dechra Ltd

Teva-Domperidone Gel is a registered trademark of Dechra Ltd. All rights reserved.

Figure

Teva-Domperidone pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Teva-Domperidone available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Teva-Domperidone destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Teva-Domperidone Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Teva-Domperidone pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. "domperidone". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  2. "domperidone". http://www.drugbank.ca/drugs/DB0118... (accessed August 28, 2018).
  3. "5587267Z69: The UNique Ingredient Identifier (UNII) is an alphanumeric substance identifier from the joint FDA/USP Substance Registration System (SRS).". https://www.fda.gov/ForIndustry/Dat... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Teva-Domperidone?

Depending on the reaction of the Teva-Domperidone after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Teva-Domperidone not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Teva-Domperidone addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Teva-Domperidone, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Teva-Domperidone consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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