SYNCROPROST 0.250 mg/ml Solution for Injection:

1. Product Overview

SYNCROPROST is a solution for injection containing 0.250 mg/ml of cloprostenol, a synthetic analogue of prostaglandin F2α ¹. This veterinary medicinal product is indicated for use across a range of livestock species, including cattle (cows and heifers), horses (mares), pigs (sows and gilts), and goats (does), for various reproductive management purposes ¹. The formulation is designed for intramuscular administration ³. The broad applicability of cloprostenol across these diverse species underscores the fundamental role of prostaglandin pathways in regulating reproductive cycles in mammals. This multi-species utility makes SYNCROPROST a versatile tool for veterinary practitioners and livestock producers aiming to optimize reproductive efficiency.

2. Qualitative and Quantitative Composition

Each milliliter of SYNCROPROST contains 0.250 mg of cloprostenol as the active substance, which is equivalent to 0.263 mg of cloprostenol sodium ¹. The use of the sodium salt form is common in pharmaceutical preparations to enhance properties such as solubility and stability, which are crucial for an injectable solution. For a comprehensive list of the inactive ingredients (excipients) present in the formulation, users should consult the product’s official leaflet ¹. The pharmaceutical form of SYNCROPROST is a solution intended for injection ¹.

3. Mechanism of Action

Cloprostenol, the active component of SYNCROPROST, is a synthetic analogue of the naturally occurring prostaglandin F2α (PGF2α) ¹. It functions primarily as a potent luteolytic agent, meaning it induces the regression, or luteolysis, of the corpus luteum ¹. The corpus luteum is a temporary endocrine gland in the ovary that produces progesterone, a hormone essential for maintaining pregnancy. By causing its regression, cloprostenol effectively reduces progesterone levels. Furthermore, cloprostenol exhibits a contractile effect on smooth muscles found in various tissues, including the uterus, gastrointestinal tract, respiratory tract, and the vascular system ¹. The influence of cloprostenol on pregnancy is directly attributed to its luteolytic property ¹. Notably, cloprostenol does not possess any androgenic, oestrogenic, or anti-progesterone activity, indicating a relatively specific action on the luteal tissue and smooth muscle ¹. Unlike certain other prostaglandin analogues, cloprostenol does not exhibit thromboxane A2 activity and, therefore, does not cause platelet aggregation ¹. This pharmacological profile explains the effectiveness of cloprostenol in manipulating reproductive events that are dependent on the presence and function of the corpus luteum.

4. Indications for Use

SYNCROPROST is indicated for specific reproductive management purposes in cattle, horses, pigs, and goats:

• Cattle (cows and heifers):
  • Induction of luteolysis, facilitating the resumption of oestrus and ovulation in cyclic females when administered during the dioestrus phase of their cycle ¹.
  • Synchronization of oestrus within a 2 to 5 day window in groups of cyclic females when treated concurrently ¹.
  • Treatment of suboestrus, also known as “silent heat,” and uterine disorders such as endometritis and pyometra that are associated with a functioning or persistent corpus luteum ¹.
  • Management of ovarian luteal cysts ¹.
  • Induction of abortion in pregnancies up to 150 days of gestation ¹.
  • Expulsion of mummified foetuses ¹.
  • Induction of parturition at or near the end of gestation ¹.
• Horses (mares):
  • Induction of luteolysis in mares that have a functional corpus luteum ¹.
  • Induction of the oestrus cycle during the breeding season ¹.
• Pigs (sows and gilts):
  • Induction of luteolysis and subsequent parturition in sows and gilts after day 114 of gestation ¹. The precise timing of administration is critical in this indication.
• Goats (does):
  • Synchronization of oestrus in does ¹.

The diverse range of these indications highlights the versatile role of cloprostenol in managing various aspects of reproduction across different livestock species. The specific timing and conditions mentioned for each indication are crucial for ensuring the product’s effectiveness and the safety of the animals.

5. Dosage and Administration

SYNCROPROST is administered via intramuscular injection. Strict adherence to aseptic techniques is necessary during administration ⁴. The dosage varies depending on the target species and the specific indication:

• Cattle:
  • For oestrus synchronization, the recommended dose is 2 ml per animal, administered twice with an interval of 11 to 14 days between injections ¹.
  • For the treatment of suboestrus and uterine disorders, a single dose of 2 ml per animal is administered, ideally before 60 days post-partum. If needed, a second treatment can be given after 10 to 11 days ¹.
  • For the induction of abortion, a single dose of 2 ml per animal is administered at any point up to 150 days after insemination ¹.
  • For the induction of parturition, a single dose of 2 ml per animal is administered within 10 days prior to the anticipated calving date. It is advisable to administer the injection as close as possible to the expected date of calving, but not more than 10 days before ¹.
• Horses:
  • For ponies, the dosage is 0.5 to 1 ml per animal, corresponding to 0.125 to 0.250 mg of cloprostenol ¹.
  • For light horses, the recommended dose is 1 ml per animal (0.25 mg cloprostenol) ¹.
  • Heavy horses should receive 2 ml per animal (0.500 mg cloprostenol) ¹.
  • If signs of oestrus are not observed, the treatment can be repeated 14 days after the initial injection ¹.
• Pigs:
  • The recommended dose for inducing parturition is 0.7 ml per animal (0.175 mg cloprostenol) administered as a single injection one or two days before the expected farrowing date ¹. It is advised to use a needle with a minimum length of 4 cm for administration ¹.
• Goats:
  • For oestrus synchronization, a single dose of 0.4 to 0.8 ml per animal (0.100 to 0.200 mg cloprostenol) is administered ¹. If no signs of oestrus are evident, the treatment may be repeated after 9 to 10 days ¹.

For multi-dose vials, it is generally recommended that the vial is not punctured more than 10 times and that the appropriate vial size is selected based on usage needs ⁴. For larger vials (50 ml and 100 ml), the use of automatic syringe equipment or a draw-off needle is advised to prevent excessive puncturing of the stopper and maintain the sterility of the product ⁴.

6. Contraindications

SYNCROPROST should not be used under certain conditions:

• General (all species):
  • Administration to pregnant animals is contraindicated unless the intended outcome is the termination of the pregnancy ¹.
  • It should not be used in animals suffering from cardiovascular, gastro-intestinal, or respiratory problems ¹.
  • Intravenous administration is strictly contraindicated ¹.
  • Animals with a known hypersensitivity to cloprostenol or any of the excipients should not receive this product ¹.
• Cattle: Induction of parturition should not be attempted in cases of suspected dystocia due to mechanical obstruction or if complications are anticipated due to abnormal foetal positioning ¹.
• Pigs: Similar to cattle, SYNCROPROST should not be used to induce parturition in pigs with suspected dystocia or abnormal foetal presentation ¹. Additionally, it is contraindicated in animals with spastic diseases of the respiratory or gastrointestinal tract ⁷.

These contraindications are essential for ensuring the safe and appropriate use of SYNCROPROST in the target animal populations.

7. Warnings and Precautions

The use of SYNCROPROST requires careful consideration of several warnings and precautions for both the animals being treated and the individuals handling the product:

• For Animals:
  • In cattle where oestrus induction is the goal, diligent heat detection is necessary starting from the second day following the injection ¹.
  • Induction of parturition or abortion in cattle may elevate the risk of complications such as retained placenta, foetal death, and metritis ¹. A higher incidence of retained foetal membranes is expected when parturition is induced ⁵.
  • In pigs, inducing parturition before day 114 of gestation can lead to an increased risk of stillbirths and may necessitate manual assistance during farrowing ¹. Using the product more than two days prior to the average gestation length calculated from farm records may also increase the number of non-viable piglets ⁷. The response to induction in sows and gilts can vary based on their physiological state, and uniform responses should not be expected across herds or individuals ⁷.
  • To minimize the risk of anaerobic infections, which might be associated with the pharmacological properties of prostaglandins, injection through contaminated skin areas should be avoided. Injection sites must be thoroughly cleaned and disinfected before administration ¹. Bacterial infections are more likely if anaerobic bacteria are introduced into the injection site ¹.
  • All animals treated with SYNCROPROST should be adequately supervised after administration ¹.
  • In cattle, there is a period of approximately four to five days after ovulation during which they are less responsive to the luteolytic effects of prostaglandins ⁴. For termination of pregnancy in cattle, the best outcomes are generally achieved before 100 days of gestation ⁴.
  • In cattle undergoing breeding programs involving SYNCROPROST, attention should be paid to their diet and overall condition. Sudden changes in feeding, feed composition, housing, or regrouping, which could cause stress, should be avoided around the time of treatment ⁵. If artificial insemination is planned, the quality of the semen and the insemination technique should be ensured beforehand ⁵.
• For Handlers:
  • Prostaglandins of the F2α type, including cloprostenol, can be absorbed through human skin and mucous membranes and may potentially cause bronchospasm or miscarriage. Therefore, direct contact with the product should be avoided ¹.
  • Benzyl alcohol, an excipient in SYNCROPROST, may cause allergic reactions in sensitive individuals. People with known hypersensitivity to benzyl alcohol should avoid contact with the product ¹.
  • Care must be taken to prevent accidental self-injection or skin contact with the product ¹.
  • Pregnant women, women of child-bearing age, individuals with asthma, and those with other respiratory conditions should exercise extreme caution when handling SYNCROPROST ¹.
  • Disposable, impervious gloves should always be worn when administering the product ¹.
  • Any accidental spillage of the product onto the skin should be washed off immediately with soap and water ¹.
  • In the event of accidental self-injection or spillage onto the skin, immediate medical attention should be sought, particularly if shortness of breath occurs. The product’s package leaflet or label should be shown to the physician ¹.
  • Hands should be thoroughly washed after using the product ¹. Eating, drinking, or smoking while handling the product is not recommended ⁷. This veterinary medicinal product may cause hypersensitivity (allergic) reactions in some individuals ⁷.

These warnings and precautions are crucial for the safe and effective use of SYNCROPROST, minimizing risks to both the animals and the handlers.

8. Adverse Reactions

Following the administration of SYNCROPROST, certain adverse reactions may occur in animals:

• Horses: Transient slight sweating and muscle tremors may be observed, which typically resolve spontaneously without the need for treatment. Some horses may also pass soft feces shortly after administration. Other potential reactions include an increase in heart and respiratory rates, abdominal discomfort, incoordination of movement, and lying down. These effects are generally seen within 15 minutes of injection and usually disappear within one hour. Mares typically continue to eat normally throughout this period ¹.
• Cattle: When SYNCROPROST is used to induce parturition, there may be an increased incidence of retained placenta, depending on the timing of the treatment relative to the date of conception ¹.
• General (all species): In very rare instances, anaphylactic-type reactions may occur, which can be life-threatening and require immediate medical intervention ¹. Infection at the injection site, characterized by swelling and crepitus, may also occur due to the introduction of anaerobic bacteria ⁶.
• Pigs: Very rarely, anaphylactic-type reactions have been reported. The frequency of injection site infections is undetermined. Additionally, transient erythema and pruritus (redness and itching of the skin), increased urination and defecation, ataxia (loss of coordination), hyperpnea (abnormally rapid breathing), dyspnea (difficulty breathing), nest-building behaviors, abdominal muscle spasms, vocalization, and salivation may occur following administration ⁷.

While SYNCROPROST is generally considered safe, awareness of these potential adverse reactions is important for monitoring animals post-treatment and providing appropriate care if necessary.

9. Withdrawal Periods

To ensure food safety, specific withdrawal periods are required following the administration of SYNCROPROST:

These short withdrawal periods, particularly the zero-day withdrawal for milk in cattle, horses, and goats, are advantageous for livestock producers as they minimize disruption to production following treatment.

10. Storage Conditions

SYNCROPROST should be stored in its original outer carton to protect it from light ¹. While specific temperature storage requirements are generally not mandated, it is advisable not to store the product above 25°C ⁴. After the first opening of the immediate packaging (vial), the shelf life of the product is 28 days ⁴. Proper storage conditions are essential to maintain the efficacy and quality of the veterinary medicinal product.

11. Manufacturer

The marketing authorization for SYNCROPROST is held by Ceva Sante Animale ⁸. This company is responsible for the quality, safety, and efficacy of the product.

12. Available Presentations

SYNCROPROST is available in various presentations, including boxes containing one 10-ml vial, one 20-ml vial, or ten 20-ml vials ¹. It is also available in boxes with one 50-ml vial and one 100-ml vial ⁸. However, it is important to note that not all pack sizes may be available in every market ¹. A common presentation is the 20-ml vial ². The availability of different vial sizes allows users to select the most suitable option based on their specific needs and the number of animals being treated.

Conclusion

SYNCROPROST 0.250 mg/ml solution for injection provides a versatile and effective tool for managing reproduction in cattle, horses, pigs, and goats. Its active ingredient, cloprostenol, acts as a potent luteolytic agent, enabling the manipulation of the oestrous cycle, induction of parturition and abortion, and treatment of certain reproductive disorders. While generally safe, careful attention to dosage, administration techniques, contraindications, and warnings is crucial for maximizing its benefits and minimizing potential risks to both animals and handlers. The short withdrawal periods associated with SYNCROPROST are advantageous for livestock production. Users should always consult the official product literature and their veterinarian for specific guidance on the appropriate use of this veterinary medicinal product.