Elephant specific information, if available, is in blue.

Chemistry/Storage/Stability/Compatibility – An alpha2-adrenergic agonist, medetomi­dine occurs as a white or almost white crystalline substance. It is soluble in water. While the compound exists as two stereoisomers, only thed-isomer is active.

The commercially available injection should be stored at room temperature (15-30°C) and protected from freezing.

Pharmacology – An alpha adrenergic receptor, medetomidine has an alpha2:alpha1 selec­tivity factor of 1620, and when compared to xylazine is reportedly 10X more specific for alpha2 receptors versus alpha1 receptors. The pharmacologic effects of medetomidine in­clude: depression of CNS (sedation), GI (decreased secretions, varying affects on intesti­nal muscle tone) and endocrine functions, peripheral and cardiac vasoconstriction, brady­cardia, respiratory depression, diuresis, hypothermia, analgesia, muscle relaxation, blanched or cyanotic mucous membranes and anxiolytic effects. Effects on blood pressure are variable.

Uses/Indications – Medetomidine is labeled for use as a sedative and analgesic in dogs over 12 weeks of age to facilitate clinical examinations and procedures, minor surgical procedures  not requiring muscle relaxation, and minor dental procedures not requiring intubation. The manufacturer recommends the IV route of administration for dental proce­dures.

Medetomidine has also been used in cats, primarily in Europe. But there is apparently much less data available to evaluate its use; caution is advised.

Pharmacokinetics – After IV or IM injection, onset of effect is rapid (5 mins. for IV; 10-15 mins. for IM). After subQ injection, responses are unreliable and this method of admin­istration cannot be recommended. The drug is absorbed via the oral mucosa when adminis­tered sublingually in dogs, but efficacy at a given dose may be less than IM dosing.

Contraindications/Precautions/Reproductive Safety – The label states that medetomi­dine is contraindicated in dogs having the following conditions: cardiac disease, respira­tory disorders, liver or kidney diseases, shock, severe debilitation, or dogs stressed due to heat, cold or fatigue.

Dogs that are extremely agitated or excited may have a decreased response to medetomi­dine, the manufacturer suggests allowing these dogs to rest quietly before administration of the drug.

Dogs not responding to medetomidine should not be re-dosed. Use in very young or older dogs should be done with caution.

The drug is not recommended to be used in pregnant dogs or those used for breeding purposes as safety data for use during pregnancy is insufficient; therefore use only when the benefits clearly outweigh the drug’s benefits.

Adverse Effects/Warnings – The adverse effects reported with medetomidine are basi­cally an extension of its pharmacologic effects including bradycardia, occasional AV blocks, decreased respiration, hypothermia, urination, vomiting, hyperglycemia, and pain on injection (IM). Rare effects have also been reported, including prolonged sedation, paradoxical excitation, hypersensitivity, apnea and death from circulatory failure.

Overdosage – Single doses of up to 5X (IV) and 10X (IM) were tolerated in dogs, but ad­verse effects can occur (see above). Death has occurred rarely in dogs (1 in 40,000) receiv­ing 2X doses.

Because of the potential of additional adverse effects occurring (heart block, PVC’s or tachycardia), treatment of medetomidine-induced bradycardia with anticholinergic agents (atropine or glycopyrrolate) is often not recommended. Atipamezole is probably a safer choice to treat any medetomidine-induced effect.

Drug Interactions – Note: Before attempting combination therapy with medetomidine, it is strongly advised to access references from veterinary anesthesiologists familiar with the use of this product.

When propofol is used after medetomidine, hypoxemia may occur. Dosage adjustments may be required along with adequate monitoring. Enhancement of sedation and analgesia may occur when medetomidine is used concurrently with fentanyl, butorphanol or meperidine, but adverse effects may be pronounced as well. Reduced dosages and moni­toring is advised if contemplating combination therapy. The use of atropine or glycopy­rrolate to prevent or treat medetomidine-caused bradycardia is controversial as tachycar­dia and hypertension may result.

Doses –

Elephants:

CAUTION!  Sedative and anesthetic drug dosages for African elephants often vary from those for Asian elephants.  Do not assume that the recommendations for one species can be applied to the other.  Significant variation may also occur between individual elephants.  Higher doses may be needed in wild or excited animals. Unless otherwise specified, doses refer to captive elephants.  The information provided here should be used as a guideline only.  Consultation with experienced colleagues is advised.

a) 3-5 µg/kg IM (Sarma et.al 2002).

b) 0.009 ± 0.002 mg/kg medetomidine in combination with 0.03 ± 0.007 mg/kg butorphanol for standing sedation in African elephants. The addition of hyaluronidase reduces time to full sedation – see abstract below. (pharmacokinetic study) 

Elephant References:

a) Sarma,B., Pathak,S.C., and Sarma,K.K. 2002. Medetomidine a novel immobilizing agent for the elephant (Elephas maximus). Res Vet Sci 73:(3):315-317

Abstract: Medetomidine was injected by the intramuscular route at the rates of 3 and 5 micrograms/kg body weight into two groups of Indian elephants (Elephas maximus). Sedation was induced at 6.20 (0.81) and 5.90 (0.60) min respectively after injection. The duration of anaesthesia was 66.20 (10.4) and 134.20 (24.12) min, respectively and recovery occurred at 125.80 (25.23) and 205.89 (29.3) min. The notable signs of sedation exhibited by the elephants were protrusion of penis, complete relaxation of trunk, flaccidity of tail and drooping of the ears with a head down position. During sedation, physiological parameters recorded were bradycardia, decreased respiration and hypothermia.

b) Luders I, Tindall B, Young D, van der Horst G, Botha S, Luther I, Maree L, Bertschinger HJ: Standing sedation with medetomidine and butorphanol in captive African elephants (Loxodonta africana). Veterinary journal (London, England : 1997) 2016, 209:190-192.

Abstract:
Doses for standing sedation allowing for various procedures in otherwise inaccessible, untrained captive African elephant bulls are presented. Thirty-three standing sedations were performed in 12 males aged 8–30 years (one to four sedations per animal). Each bull received a combination of 0.009 ± 0.002 mg/kg medetomidine and 0.03 ± 0.007 mg/kg butorphanol. Full sedation was reached on average 25.5 min after injection. The addition of hyaluronidase (1000–2000 IU) significantly reduced time to full sedation to 16.5 min (paired t test, P = 0.024). Reversal was induced with intramuscular atipamezole 0.008 (±0.002) and naltrexone 0.035 (±0.015) mg/kg. Recovery took on average 7 min (3–18 min). The medetomidine/butorphanol combination provided safe standing sedation for smaller procedures.

Monitoring Parameters – Level of sedation and analgesia; heart rate; body temperature. Additionally, heart rhythm, blood pressure, respiration rate and pulse oximetry should be considered, particularly in higher risk patients if the drug is to be used.

Client Information – This drug should be administered and monitored by veterinary pro­fessionals only. Clients should be made aware of the potential adverse effects associated with its use, particularly in dogs at risk (older, preexisting conditions).

Dosage Forms/Preparations/FDA Approval Status –

Veterinary-Approved Products:

Medetomidine HCl for Injection 1 mg/ml in 10 ml multidose vials; Domitor®  (Pfizer); (Rx) Approved for use in dogs.