Pharmacological Action

Etorphine is a highly potent, semi-synthetic opioid derivative of oripavine and is classified as a pure agonist. It acts stereospecifically on µ-, δ- and κ-opioid receptors, inducing catatonia associated with total analgesia at very low doses.

Pharmacokinetic and Pharmacodynamic Properties

Following intramuscular administration of optimal doses, onset of action in most wildlife species is observed within 2–8 minutes, with the full effect reached in 15–30 minutes.

In rodents, the analgesic effect peaks sharply at 15 minutes with a duration of action of approximately 50 minutes.

In elephants, peak serum concentration is reached 30 minutes after intramuscular injection with a half-life of 66 minutes and clearance of 13,6 ml/min/kg.

Etorphine is primarily eliminated in the bile and excreted in the faeces, with some excretion occurring in the urine. Full recovery from the effects of etorphine can take up to 7–8 hours if an opioid antagonist is not administered.

Re-cycling of etorphine via enterohepatic circulation or redistribution from adipose depots may lead to re-narcotisation of the animal.

Indications

CAPTIVON is indicated for reversible narcosis with analgesia in wildlife animals.

Contraindications

CAPTIVON is contraindicated in domestic animals and wild felids.

Warnings

The safety of CAPTIVON in pregnant and lactating wildlife animals has not been established. There is a risk of respiratory depression in the newborn if CAPTIVON is given to a parturient animal.

Rodent studies have shown that etorphine readily crosses the placental barrier. Etorphine administered in pregnant rats results in respiratory depression in the mother and depressed oxygen uptake in the newborn rats that is directly proportional to the maternal dose.

CAPTIVON residue studies have not been conducted in wildlife animals and consequently, human and predator consumption of carcasses from animals treated with CAPTIVON is not advisable.

Dosage and Directions for Use

CAPTIVON dosing is dependent on species, body mass and the condition of the wildlife animal being treated, and doses should be adjusted accordingly.

Administration by intravenous or intramuscular injection is recommended. Refer to the recommended dosage table below.

The effect of CAPTIVON may be reversed by administering ACTIVON at a ratio of 3–5 mg of ACTIVON for every 1 mg of CAPTIVON used in elephant, rhino or giraffe, and for other wildlife at a ratio of 2–3 mg of ACTIVON for every 1 mg of CAPTIVON used.

Side Effects and Special Precautions for Use

The most serious adverse effect following CAPTIVON administration is respiratory depression, usually observed within the first five minutes after administration. CAPTIVON should be reversed as soon as possible in cases of severe respiratory depression, and animals should not remain immobilised for longer than necessary to avoid complications.

The use of CAPTIVON in elderly, diseased, emaciated and highly stressed animals carries a greater degree of risk. Precautionary measures should be taken, including maintenance of airways and prevention of hyperthermia.

In equids and rhino, CAPTIVON may result in a dramatic rise in blood pressure, tachycardia, hyperpyrexia and pronounced muscle tremors. Administration in rhino may lead to hypoventilation, hypoxaemia and metabolic acidosis.

Significant hypertension due to an increase in total peripheral resistance, and moderate to severe bradycardia, has been reported in ungulate species. Excitement, increased muscle tone and resulting hyperthermia is particularly common in ungulates.

Passive regurgitation of rumen contents is common and ruminants should be kept in sternal recumbency with heads lifted and tilted downwards to prevent aspiration pneumonia. Under-dosing may cause hyper-excitability, hyperventilation and severe alkalosis.

Accidental exposure to CAPTIVON could have serious effects on humans due to the potency and high concentration of the medicine.

The following precautions should be taken by veterinarians when using CAPTIVON:

• Do not work with CAPTIVON unaccompanied.
• Wear gloves when handling CAPTIVON.
• Ensure water or an appropriate irrigation solution is available to treat accidental exposure of the skin or eyes.
• Eye protection should be used where there is a risk of CAPTIVON splashing into the eyes.
• Ensure that the antidote, naloxone, and a needle and syringe for administration are readily available.
• An assistant capable of administering the antidote to humans should be present at all times and fully briefed on the procedure to follow in the event of accidental exposure.
• Once the required dose has been withdrawn from the vial, immediately discard the needle into a closed container or sharps bin.
• CAPTIVON should not be used in blowpipes or similar devices where the medicine solution is pressurised.
• The lethal CAPTIVON dose in humans is estimated to be between 30–120 µg.
• Symptoms of toxicity in humans include dizziness, nausea, pinpoint pupils, respiratory depression, hypotension, loss of consciousness and cardiac arrest.
• In the event of accidental topical exposure of the skin or eyes, wash the affected area immediately with copious amounts of water and monitor for symptoms of toxicity.
• Should accidental injection occur, seek medical attention immediately. Inject 0,8–1,2 mg naloxone intramuscularly or intravenously and repeat at 2–3 minute intervals until symptoms are reversed. Monitor airway and ventilation and initiate CPR as necessary until medical help arrives.

Known Symptoms of Overdosage and Particulars of Its Treatment

CAPTIVON toxicity in wildlife animals results in respiratory depression and cardiac suppression. Primates, hippopotamus and rhinos are particularly sensitive to CAPTIVON.

An overdose can be treated with ACTIVON (diprenorphine hydrochloride) and with analeptics such as doxapram hydrochloride. Oxygen supplementation is recommended in cases of severe respiratory depression.

BUTADYNE 50 (butorphanol tartrate) may be used to partially reverse respiratory depression and to lighten the plane of anaesthesia of large species such as rhino. In the latter case, the animals may be walked under sedation onto vehicles for transport.

Identification

A clear, colourless solution free from visible particulate matter.

Presentation

CAPTIVON 49 and CAPTIVON 98 is supplied in a 10 ml amber vial, filled to 5 ml, with a grey stopper and a white plastic cap.

Storage Instructions

Store at or below 25 °C.

Do not refrigerate.

Protect from light.

Once the rubber stopper has been pierced, the contents of the vial should be used within two weeks.

KEEP OUT OF REACH OF CHILDREN AND UNINFORMED PERSONS.

Registration Numbers

CAPTIVON 49: 93/1.3.1/9

CAPTIVON 98: 93/1.3.1/10

Holder of the Certificate of Registration

Wildlife Pharmaceuticals (Pty) Ltd
38 Wilken Street
Rocky Drift
White River
1240
South Africa

Date of Publication

19 December 2024

Recommended CAPTIVON Doses

Recommended CAPTIVON doses, alone or in combination with other medicines, based on literature and field efficacy data.

Dosage Table Notes

ɸ Higher dose range recommended for nervous or excited animals, or immobilisation where a short induction period is needed. Lower dose range recommended for weak, sick, debilitated or tame animals, where longer induction times are allowable, for animals in captivity, or where movement is restricted, for example in zoos.

¥ The level of opioid anaesthesia can be decreased to the desired level by concurrent intravenous administration of BUTADYNE 50 (butorphanol tartrate).

* The higher dosage range is recommended for smaller animals.