Active ingredient: Butorphanol Tartrate - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Analgesics, Opioid
• Antitussive Agents
• Narcotic Antagonists
• Narcotics

Dosage Forms

• Drops
• Drug premix
• Gel
• Globules
• Liquid
• Powder for solution
• Solution
• Spray
• Tablet

Brands / Synonyms

Butorfanol; Butorfanol [INN-Spanish]; Butorphanol; Butorphanol Tartrate Preservative Free; Butorphanol [USAN:BAN:INN]; Butorphanolum [INN-Latin]; DEA No. 9720; Stadol; Stadol Preservative Free

Indications

For the management of pain when the use of an opioid analgesic is appropriate. Also indicated as a preoperative or preanesthetic medication, as a supplement to balanced anesthesia, and for the relief of pain during labor.

Pharmacology

Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord.

Mechanism of Action

Butorphanol is a mixed agonist-antagonist with low intrinsic activity at receptors of the µ-opioid type (morphine-like). It is also an agonist at k-opioid receptors. Its interactions with these receptors in the central nervous system apparently mediate most of its pharmacologic effects, including analgesia.

Absorption

Rapidly absorbed after intramuscular injection and peak plasma levels are reached in 20-40 minutes. The absolute bioavailability is 60-70% and is unchanged in patients with allergic rhinitis. In patients using a nasal vasoconstrictor (oxymetazoline) the fraction of the dose absorbed was unchanged, but the rate of absorption was slowed. Oral bioavailability is only 5-17% because of extensive first-pass metabolism.

Toxicity

The clinical manifestations of butorphanol overdose are those of opioid drugs in general. The most serious symptoms are hypoventilation, cardiovascular insufficiency, coma, and death.

Biotrnasformation / Drug Metabolism

Extensively metabolized in the liver. The pharmacological activity of butorphanol metabolites has not been studied in humans; in animal studies, butorphanol metabolites have demonstrated some analgesic activity.

Contraindications

STADOL Injection and STADOL NS are contraindicated in patients hypersensitive to butorphanol tartrate or the preservative benzethonium chloride in STADOL NS or STADOL Injection in the multi-dose vial.

Drug Interactions

Concurrent use of butorphanol with central nervous system depressants (e.g., alcohol, barbiturates, tranquilizers, and antihistamines) may result in increased central nervous system depressant effects. When used concurrently with such drugs, the dose of butorphanol should be the smallest effective dose and the frequency of dosing reduced as much as possible when administered concomitantly with drugs that potentiate the action of opioids.

In healthy volunteers, the pharmacokinetics of a 1-mg dose of butorphanol administered as STADOL NS were not affected by the coadministration of a single 6-mg subcutaneous dose of sumatriptan. However, in another study in healthy volunteers, the pharmacokinetics of butorphanol were significantly altered (29% decrease in AUC and 38% decrease in C_max) when a 1-mg dose of STADOL NS was administered 1 minute after a 20-mg dose of sumatriptan nasal spray. (The two drugs were administered in opposite nostrils.) When the STADOL NS was administered 30 minutes after the sumatriptan nasal spray, the AUC of butorphanol increased 11% and C_max decreased 18%.

In neither case were the pharmacokinetics of sumatriptan affected by coadministration with STADOL NS. These results suggest that the analgesic effect of STADOL NS may be diminished when it is administered shortly after sumatriptan nasal spray, but by 30 minutes any such reduction in effect should be minimal.

The safety of using STADOL NS and IMITREX® (sumatriptan) Nasal Spray during the same episode of migraine has not been established. However, it should be noted that both products are capable of producing transient increases in blood pressure.

The pharmacokinetics of a 1-mg dose of butorphanol administered as STADOL NS were not affected by the coadministration of cimetidine (300 mg QID). Conversely, the administration of STADOL NS (1 mg butorphanol QID) did not alter the pharmacokinetics of a 300-mg dose of cimetidine.

It is not known if the effects of butorphanol are altered by concomitant medications that affect hepatic metabolism of drugs (erythromycin, etc.), but physicians should be alert to the possibility that a smaller initial dose and longer intervals between doses may be needed.

The fraction of STADOL NS absorbed is unaffected by the concomitant administration of a nasal vasoconstrictor (oxymetazoline), but the rate of absorption is decreased. Therefore, a slower onset can be anticipated if STADOL NS is administered concomitantly with, or immediately following, a nasal vasoconstrictor.

No information is available about the use of butorphanol concurrently with MAO inhibitors.