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Dinoprost Tromethamine

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

Chemistry - The tromethamine (THAM) salt of the naturally occurring prostaglandin F2 alpha , dinoprost tromethamine  occurs as a white to off-white, very hygroscopic, crystalline powder with a melting point of about 100°C. One gram is soluble in about 5 ml of water. 1.3 micrograms of dinoprost tromethamine is equivalent to 1 micrograms of dino­prost. Dinoprost tromethamine may also be known as dinoprost trometamol , PGF2 alpha THAM , or prostaglandin F2 alpha tromethamine .

 

Storage/Stability/Compatibility - Dinoprost for injection should be stored at room tem­perature (15-30°C) in airtight containers. The human-approved product is recommended to be stored under refrigeration. Dinoprost is considered to be relatively insensitive to heat, light, and alkalis.

 

Pharmacology - Prostaglandin F2alpha has several pharmacologic effects on the female reproductive system, including stimulation of myometrial activity, relaxation of the cervix, inhibition of steroidogenesis by corpora lutea, and can potentially lyse corpora lutea.

 

Uses/Indications - Lutalyse®  (Upjohn) is labeled for use in cattle as a luteolytic agent for estrous synchronization, unobserved (silent) estrous in lactating dairy cattle, pyometra, and as an abortifacient in feedlot and non-lactating dairy cattle. It is labeled in swine to act as a parturitient inducing agent. The product is labeled for use in mares as a luteolytic agent to control the time of estrus in cycling mares and to assist in inducing estrus in “difficult to breed mares.”

 

Unlabeled uses of dinoprost include its use in small animals as an abortifacient agent and as adjunctive medical therapy in pyometra. Although not approved, dinoprost is used also in sheep and goat reproductive medicine.

 

Pharmacokinetics - In studies done in rodents, dinoprost was demonstrated to distribute very rapidly to tissues after injection. In cattle, the serum half-life of dinoprost has been stated to be only “minutes” long.

 

Contraindications/Precautions - Unless being used as an abortifacient or parturition in­ducer, dinoprost should not be used during pregnancy in all species. Dinoprost is contraindicated in animals with bronchoconstrictive respiratory disease (e.g., asthma, “heavey” horses). It should not be administered intravenously.

 

In swine, dinoprost should not be administered prior to 3 days of normal predicted farrowing as increased neonatal mortality may result.

 

According to the manufacturer, dinoprost is contraindicated in mares with acute or subacute disorders of the vascular system, GI tract, respiratory system or reproductive tract.

 

Dinoprost should be used with extreme caution, if at all, in dogs or cats greater than 8 years old, or with preexisting cardiopulmonary or other serious disease (liver, kidney, etc.). Some clinicians regard closed-cervix pyometra as a relative contraindication to the use of dinoprost.

 

Adverse Effects/Warnings - In cattle, increased temperature has been reported when administered in overdose (5-10X recommended doses) quantities. Limited salivation and bacterial infections at the injection site have been reported. If administered intravenously, increased heart rates have been noted.

 

In mares, transient decreased body (rectal) temperature and sweating have been reported most often. Less frequently, increased respiratory and heart rates, ataxia, abdominal pain and lying down have also been noted. These effects are generally seen within 15 minutes of administration and resolve within an hour.

 

In swine, dinoprost has caused erythema and pruritis, urination, defecation, slight ataxia, hyperpnea, dyspnea, nesting behavior, abdominal muscle spasms, tail movements, increased vocalization and salivation. These effects may last up to 3 hours. At doses of 10 times recommended, vomiting may be seen in swine.

 

In dogs and cats, dinoprost can cause abdominal pain, emesis, defecation, urination, pupillary dilation followed by constriction, tachycardias, restlessness and anxiety, fever, hypersalivation, dyspnea and panting. Cats may also exhibit increased vocalization and intense grooming behavior. Severity of effects is generally dose dependent. Defecation can be seen even with very low dosages. Reactions generally appear in 5-120 minutes after administration and may persist for 20-30 minutes. Fatalities have occurred (especially in dogs) after use. Dogs and cats should be monitored for cardiorespiratory effects, especially after receiving higher dosages.

When used as an abortifacient in humans, dinoprost causes nausea, vomiting or diarrhea in about 50% of patients.

 

Overdosage - Dogs are apparently more sensitive to the toxic effects of dinoprost than other species. The LD50 in the bitch has been reported to be 5.13 mg/kg after SQ injection which may be only 5X greater than the recommended dose by some clinicians. In cattle, swine, and horses, dinoprost’s effects when administered in overdose quantities are outlined above in the Adverse effects section. If symptoms are severe in any species and require treatment; supportive therapy is recommended.

 

Drug Interactions - Other oxytocic agents’ activity may be enhanced by dinoprost. Reduced effect of dinoprost would be expected with concomitant administration of a progestin.

 

Doses -

Horses:

To induce cyclic activity in animals who are acyclic due to persistent corpus lutea:

a)   5 mg IM; most effective in mares with corpora lutea older than 5 days and who have progesterone levels >1 ng/ml (4 ng/ml even better). (Rossdale 1987)

 

For difficult to breed mares secondary to progesterone levels consistent with the presence of a functional corpus luteum:

a)   1 mg per 45 kg body weight IM (Package Insert; Lutalyse®—Upjohn)

 

For controlling time of estrus of estrous cycling mares:

a)   1 mg per 45 kg body weight IM. When treated during diestrus, most mares re­turn to estrus in 2-4 days and ovulate 8-12 days after treatment. (Package Insert; Lutalyse®—Upjohn)

 

As an abortifacient:

a)   Prior to the 12th day of pregnancy: 5 mg IM

After the 4th month of pregnancy: 1 mg per 45 kg body weight (1 mg per 100 pounds) daily until abortion takes place. (Lofstedt 1986)

b)   From day 80-300: 2.5 mg q12h; approximately 4 injections required on average to induce abortion (Roberts 1986a)

 

For estrus synchronization in normally cycling mares:

a) Three methods:

1)   Two injection method— On day 1 give 5 mg dinoprost and again on day 16. Most (60%) mares will begin estrus 4 days after the second injection and about 90% will show estrous behavior by the 6th day after the second injection. Breed using AI every second day during estrus or inseminate at predetermined times without estrus detection. Alternatively, an IM injection of HCG (2500-3300 Units) can be added on the first or second day (usually day 21) of estrus to hasten ovulation. Breed using AI on days 20, 22, 24, and 26. This may be of more benefit when used early in the breeding season.

 

2)   Progestagen/Prostaglandin method— Give altrenogest (0.44 mg/kg) for 8-12 days PO. On last day of altrenogest therapy (usually day 10) give dinoprost (dose not noted, but suggest using same dose as “1” above). Majority of mares will show estrus 2-5 days after last treatment. Inseminante every 2 days after detection of estrus. Synchronization may be improved by giving 2500 IU of HCG IM on first or second day of estrus or 5-7 days after altrenogest is withdrawn.

 

3)   On day 1, inject 150 mg progesterone and 10 mg estradiol-17betadaily for 10 days. On last day, also give dinoprost (dose not noted, but suggest using same dose as “1” above). Perform AI on alternate days after estrus detection or on days 19, 21, and 23. (Bristol 1987)

 

Monitoring Parameters - Depending on use, see above. Monitoring for adverse effects is especially important in small animals.

 

Client Information - Dinoprost should be used by individuals familiar with its use and precautions. Pregnant women, asthmatics or other persons with bronchial diseases should handle this product with extreme caution. Any accidental exposure to skin should be washed off immediately.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times -

 

Veterinary-Approved Products:

Dinoprost Tromethamine for injection, equivalent to 5 mg/ml of dinoprost in 10 ml and 30 ml vials; Lutalyse®  (Upjohn); (Rx)  Approved for use in beef and non-lactating dairy cattle, swine and mares. No preslaughter withdrawal or milk withdrawal is re­quired when used as labeled; no specific tolerance for dinoprost residues have been published. It is not for use in horses intended for food

 

Human-Approved Products: None

 

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