Maropitant: A novel treatment for acute vomiting in dogs

Vomiting is one of the most common reasons dogs are presented for veterinary consultation.1 Most antiemetics (e.g. metoclopramide, diphen-hydramine, chlorpromazine, ondansetron, dolasetron) have been developed for use in people and are not approved for use in small animals.2 The recent introduction of maropitant citrate, which is from a novel class of antiemetics and is approved to prevent and treat acute vomiting in dogs with a variety of clinical conditions, is a major advance in managing these patients (Table 1).

Table 1 Indications and Dosages of Maropitant in Dogs*

INDICATIONS

Maropitant has been studied in dogs to treat acute vomiting associated with systemic disorders (e.g. gastroenteritis, acute pancreatitis, cholangitis) or infections (e.g. parvovirus infection except in young pups, leptospirosis) and a variety of other clinical disorders (e.g. uremia, renal failure, pyometra, diabetic ketoacidosis, hypercalcemia, adrenal insufficiency, intestinal obstruction, gastrointestinal neoplasia, linear foreign object, central nervous system disease, increased intracranial pressure, drug or toxic agent poisoning).3,4 It is also effective against vomiting due to motion sickness in dogs.5

Maropitant's efficacy and safety have been evaluated in randomized clinical trials for preventing vomiting due to motion sickness in dogs.5 Compared with a placebo, maropitant reduced vomiting by 86.1% or 76.5% when given two or 10 hours before travel, respectively.5,6 Comparatively, ondansetron is not effective against vomiting due to motion sickness.7 Maropitant is also effective in preventing and treating acute and delayed emesis in patients undergoing chemotherapy for cancer (e.g. cisplatin).8-10 Chemotherapeutic agents activate the chemoreceptor trigger zone by releasing various neurotransmitters, including substance P, both centrally and peripherally, to induce vomiting (see the sidebar titled "Maropitant's pharmacokinetics and pharmacology").3,8

DOSE AND ADMINISTRATION

To prevent acute vomiting in dogs, maropitant is given subcutaneously or orally before an anticipated emesis event and then once a day thereafter for up to five consecutive days (Table 1).3 To treat acute vomiting in dogs, 1 mg/kg maropitant is given subcutaneously once a day for up to five consecutive days.3 If you need to treat a patient after the five days, stop maropitant administration for two days, and then reinitiate therapy for up to another five days.3

To prevent motion sickness-induced vomiting, administer at least 8 mg/kg maropitant orally at least two hours before travel and once a day for up to two consecutive days.3 If longer treatment is needed, stop maropitant administration for three days, and then reinitiate therapy for up to another two days.3

Advise clients not to tightly wrap the tablets in fatty food such as cheese or meat since this may keep the tablets from dissolving and delay the effect.11 Dogs should not be fed one to two hours before receiving maropitant. It is also recommended to avoid inserting the tablets in hot dogs, sausage, or pocket-type treats.

Maropitant citrate injectable solution and tablets are used extra-label in cats for the same indications and at the same dosages as those in dogs.3

PREPARATIONS

Maropitant is FDA-approved for use only in dogs for subcutaneous injection or oral administration. It is available in the United States as Cerenia (Pfizer Animal Health) and is supplied as a tablet and an injectable solution (20-ml amber glass vials). The tablets contain 16, 24, 60, or 160 mg maropitant citrate. Each milliliter of solution contains 10 mg maropitant citrate, 63 mg sulfobutylether-beta-cyclodextrin (SBECD), and 3.3 mg metacresol as a preservative. Cyclodextrins improve water solubility and stability and reduce the toxicity of the molecules.12 Dogs receiving SBECD orally may experience gastrointestinal effects such as soft feces or diarrhea. These effects are reversible when treatment is withdrawn.13

TOXICITY

Maropitant has a low acute toxicity: the oral LD50 (free base) in rats is > 2,000 mg/kg.14 Maropitant is well-tolerated in healthy dogs receiving doses of up to three times the recommended oral dose of 8 mg/kg or for three times longer than the proposed maximum duration of treatment.3,12 In cats, maropitant is also well-tolerated at doses up to 5 mg/kg.15

Maropitant is not teratogenic in rats, but it has not been evaluated in pregnant, breeding, or lactating dogs.14 Do not administer maropitant in dogs younger than 16 weeks because bone marrow hypoplasia has been reported in puppies younger than 11 weeks.12 Also administer it with caution in dogs with hepatic dysfunction.3

ADVERSE REACTIONS

The most common adverse reactions noted during high-dose (> 8 mg/kg) clinical studies in dogs included hypersalivation, diarrhea, bloody stools, drooling, retching, lethargy, loss of appetite, muscle tremors, and flatulence.12,16 Swelling or pain at the injection site has been reported after subcutaneous administration.3,12 At high dosages, maropitant can interact with cardiac calcium channels: at a dosage of 20 mg/kg given orally once a day for 93 days, electrocardiographic changes (slight increases in P-R interval, P-wave duration, and QRS amplitude) were noted.3,17 According to the Canadian product label, use maropitant with caution in dogs with bradycardia or underlying heart disease since maropitant may increase the risk of arrhythmias.12

HANDLING PRECAUTIONS

Topical exposure may elicit localized allergic skin reactions in some people. Repeated or prolonged exposure may lead to skin sensitization.12 Direct exposure of the skin or eyes may cause allergic reactions, so avoid drug contact with the skin and eyes and wear impervious gloves during administration.

ENVIRONMENTAL ISSUES

Maropitant is degraded slowly, so avoid releasing it into the environment.14 Maropitant is also highly toxic to aquatic organisms,14 so do not allow the product to contaminate ponds, waterways, or ditches.

STORAGE AND STABILITY

Store maropitant injectable solution at a controlled room temperature of 68 to 77 F (20 to 25 C), and protect it from light.3 The injection product label states the drug should be used within 28 days of first vial puncture in accordance with FDA requirements. Maropitant tablets are packaged in foil to protect them from moisture. Tablets removed from the blister pack and halved do not lose potency within 48 hours.3

Lotfi El Bahri, DVM, MSc, PhD

Department of Pharmacology and Toxicology

École Nationale de Médecine Vétérinaire

2020 Sidi-Thabet, Tunisia

REFERENCES

1. Tams TR. A diagnostic approach to vomiting in dogs and cats. Vet Med 1992;87(8):785-792.

2. Encarnacion HJ, Parra J, Mears E, et al. Vomiting. Compend Contin Educ Pract Vet 2009;31(3):122-131.

3. Plumb DC. Maropitant citrate. Plumb's veterinary drug handbook. 6th ed. Ames, Iowa: Blackwell Publishing, 2008;558-560.

4. de la Puente-Redondo VA, Siedek EM, Benchaoui HA, et al. The anti-emetic efficacy of maropitant (Cerenia) in the treatment of ongoing emesis caused by a wide range of underlying clinical aetiologies in canine patients in Europe. J Small Anim Pract 2007;48(2):93-98.

5. Benchaoui HA, Siedek EM, de la Puente-Redondo VA, et al. Efficacy of maropitant for preventing vomiting associated with motion sickness in dogs. Vet Rec 2007;161(13):444-447.

6. Conder GA, Sedlacek HS, Boucher JF, et al. Efficacy and safety of maropitant, a selective neurokini n 1 receptor antagonist, in two randomized clinical trials for prevention of vomiting due to motion sickness in dogs. J Vet Pharmacol Ther 2008;31(6):528-532.

7. The Merck veterinary manual. 9th ed. Whitehouse Station, N.J.: Merck & Co, 1998;1683.

8. de la Puente-Redondo VA, Tilt N, Rowan TG, et al. Efficacy of maropitant for treatment and prevention of emesis caused by intravenous infusion of cisplatin in dogs. Am J Vet Res 2007;68(1):48-56.

9. Vail DM, Rodabaugh HS, Conder GA, et al. Efficacy of injectable maropitant (CERENIA) in a randomized clinical trial for prevention and treatment of cisplatin-induced emesis in dogs presented as veterinary patients. Vet Comp Oncol 2007;5(1):38-46.

10. Kitchell BE. Advances in hemangiosarcoma treatment, in Proceedings. 33rd World Small Anim Vet Assoc Congress, 2008:505-507.

11. Pfizer Animal Health. Cerenia (maropitant citrate). Available at: http://pfizerah.com/Product_Overview.aspx?drug=CR&country=US&lang=EN&species=CN. Accessed Aug. 17, 2009.

12. U.S. or Canadian product information: Cerenia, Pfizer Animal Health, U.S. and Canada.

13. Stella VJ, He Q. Cyclodextrins. Toxicol Pathol 2008;36(1):30-42.

14. Material Safety Data Sheet. Pfizer, May 2007.

15. Hickman MA, Cox SR, Mahabir S, et al. Safety, pharmacokinetics and use of the novel NK-1 receptor antagonist maropitant (Cerenia) for the prevention of emesis and motion sickness in cats. J Vet Pharmacol Ther 2008;31(3):220-229.

16. Freedom of information summary. Original New Animal Drug Application NADA 141-2621. CERENIA (maropitant citrate). Pfizer Inc. January 2007.

17. Gogny M. Principe actif: le maropitant. Nouv Prat Vét Canine Féline 2008;8(39):69-70.