Zydol

A clear and colorless solution.
Each mL contains: Butorphanol Tartrate, USP 2 mg.

Opioid Analgesic.
Pharmacology: Pharmacodynamics: The analgesic effect of butorphanol varies with the route of administration. Onset occurs within minutes when given intravenously and within 15 minutes when given by intramuscular injection.
Peak analgesic effect is reached within 30 to 60 minutes for both intravenous and intramuscular routes.
The duration of analgesia, influenced by both the pain model and administration route, generally lasts 3 to 4 hours, based on the time by which 50% of patients required re-medication. In postoperative studies, the duration of analgesia with IV or IM butorphanol was comparable to that of morphine, meperidine, and pentazocine when administered at equipotent doses.
Mechanism of Action: Butorphanol acts as a partial agonist at the mu-opioid receptor and a full agonist at the kappa-opioid receptor. Its primary therapeutic effect is analgesia. Clinically, doses are adjusted to achieve effective pain relief, though use may be limited by side effects such as respiratory and central nervous system (CNS) depression.
While the exact mechanism of its analgesic effect is unknown, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord are thought to mediate the analgesic effects of this drug.
Pharmacokinetics: Butorphanol Tartrate Injection is rapidly absorbed following intramuscular (IM) administration, with peak plasma concentrations reached within 20 to 40 minutes. After the initial absorption and distribution phase, the pharmacokinetics of butorphanol are similar for both intravenous and intramuscular administration.
Serum protein binding is independent of concentration over the range achieved in clinical practice (up to 7 ng/mL) with a bound fraction of approximately 80%.
The volume of distribution of butorphanol ranges from 305 to 901 liters and total body clearance from 52 to 154 liters/hr.
Metabolism and Elimination: Butorphanol is extensively metabolized in the liver, with similar metabolic profiles observed after both intravenous and intramuscular administration. Due to significant first-pass metabolism, oral bioavailability is low-ranging from only 5% to 17%.
The primary metabolite is hydroxybutorphanol, while norbutorphanol is formed in smaller amounts. Both metabolites are detectable in plasma, although norbutorphanol typically appears at only trace levels. Hydroxybutorphanol has an elimination half-life of approximately 18 hours, which can lead to moderate accumulation (less than 5-fold) with repeated dosing to steady state.
Elimination of butorphanol occurs through both urine and feces. Following administration of radiolabeled butorphanol, 70-80% of the dose is recovered in urine, and about 15% in feces. Only about 5% of the dose is excreted unchanged in urine, while 49% is excreted as hydroxybutorphanol and less than 5% as norbutorphanol.

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

When determining the appropriate dose of Butorphanol Tartrate Injection, several factors should be considered including age, body weight, physical condition, underlying medical issues, concurrent medications, the type of anesthesia to be used, and the nature of the surgical procedure.
Extra caution is advised when using butorphanol in elderly patients, those with hepatic or renal impairment, or during labor.
The following dosage recommendations apply to patients with normal hepatic and renal function who are not receiving other central nervous system (CNS)-active medications.
Use for Pain Relief: Intravenous (IV): The usual recommended single IV dose is 1 mg, repeated every 3 to 4 hours as needed. The effective dosage range is 0.5 to 2 mg, depending on pain severity, given every 3 to 4 hours.
Intramuscular (IM): The usual single IM dose is 2 mg, particularly in patients who can remain recumbent in case of drowsiness or dizziness. Doses may be repeated every 3 to 4 hours as necessary. The effective range is 1 to 4 mg, repeated every 3 to 4 hours. There is insufficient clinical data to support single doses exceeding 4 mg.
Use as Preoperative/Preanesthetic Medication: Preoperative dosage should be individualized. The usual adult dose is 2 mg IM, administered 60 to 90 minutes before surgery. This provides sedative effects comparable to 10 mg of morphine or 80 mg of meperidine.
Use in Balanced Anesthesia: The usual dose is 2 mg IV administered shortly before induction. During anesthesia, 0.5 to 1 mg IV may be given in increments. Doses can be increased up to 0.06 mg/kg (approximately 4 mg/70 kg), depending on prior administration of sedatives, analgesics, or hypnotics. Total doses range from 4 mg to 12.5 mg (or 0.06 mg/kg to 0.18 mg/kg), depending on individual requirements.
Use in Labor: In full-term patients in early labor, a dose of 1 to 2 mg IV or IM may be administered, and repeated after 4 hours if needed. Alternative analgesia should be used for pain associated with delivery or if delivery is expected to occur within 4 hours.
If butorphanol is used with other drugs that may enhance its effects, the lowest effective dose should be used.

Acute Overdose Symptoms: An overdose of Butorphanol Tartrate Injection can cause symptoms such as slow or difficult breathing, drowsiness progressing to stupor or coma, muscle weakness, cold skin, small pupils, and in severe cases, pulmonary edema (fluid in the lungs), slow heart rate, low blood pressure, blocked airways, unusual snoring, and possibly death. Overdose may also cause enlarged pupils due to lack of oxygen.
Overdose Treatment: Symptoms: Symptoms of butorphanol overdose are consistent with those observed with opioid overdose in general. The most serious manifestations include hypoventilation, cardiovascular insufficiency, coma, and death.
Management: In cases of suspected butorphanol overdose, primary attention should be directed toward the establishment and maintenance of adequate ventilation, peripheral perfusion, airway protection, and normal body temperature. Patients should be placed under continuous observation, with serial assessment of mental status, responsiveness, and vital signs.
Oxygen and ventilatory support should be readily available, and pulse oximetry or other appropriate monitoring should be used as indicated. In patients presenting with coma or compromised airway reflexes, endotracheal intubation or placement of another artificial airway may be required. An adequate intravenous access should be secured to facilitate treatment, including the management of hypotension associated with vasodilation.
Opioid Antagonists: The use of an opioid antagonist such as naloxone should be considered. Because the duration of action of butorphanol may exceed that of naloxone, repeated doses or a continuous infusion of naloxone may be necessary to maintain adequate reversal.

Opioid Dependence: Butorphanol is contraindicated in patients who are opioid dependent. Due to its opioid antagonist properties, butorphanol may precipitate acute opioid withdrawal characterized by anxiety, agitation, mood changes, hallucinations, dysphoria, weakness, and diarrhea.
Recent or Concurrent Use of Opioid Analgesics: Because opioid tolerance cannot be reliably assessed in patients who have recently received repeated doses of opioid analgesics, butorphanol is contraindicated in such patients due to the risk of precipitating withdrawal.
Head Injury or Increased Intracranial Pressure: Butorphanol is contraindicated in patients with head injury or elevated intracranial pressure, as its use may cause carbon dioxide retention, drug-induced miosis, and alterations in mental status that can obscure neurologic evaluation.
Significant Respiratory Impairment: Butorphanol is contraindicated in patients with significant respiratory depression or impaired respiratory function, including those receiving other CNS depressants or those with underlying CNS disease affecting respiratory control.
Cardiovascular Instability: Butorphanol is contraindicated in patients with acute myocardial infarction, ventricular dysfunction, or coronary insufficiency when an increase in cardiac workload may pose a significant risk. Severe hypertension has been reported during therapy; if it occurs, therapy must be discontinued and appropriate treatment initiated.

Butorphanol tartrate injection is an opioid analgesic that carries a risk of addiction, abuse, and misuse, even when used as prescribed. Although the exact risk of addiction varies by individual, it can occur in patients receiving appropriate therapy at recommended dosages, as well as in cases of misuse.
Before prescribing butorphanol tartrate injection, assess each patient's risk for opioid addiction, abuse, or misuse. All patients should be closely monitored for the development of these behaviors or conditions throughout treatment.
These risks are increased in patients with a personal or family history of substance use disorders (including drug or alcohol abuse or addiction) or mental health conditions such as major depression. However, the presence of such risks should not preclude the proper management of pain.
In higher-risk patients, butorphanol tartrate injection may still be appropriate. However, its use requires comprehensive counseling on the associated risks, strict adherence to prescribed usage, and enhanced monitoring for signs of misuse, abuse, or addiction.

Pregnancy: There are no sufficient, well-controlled studies on the use of Butorphanol Tartrate Injection in pregnant women before 37 weeks of pregnancy. It should only be used during pregnancy if the potential benefits to the mother outweigh the possible risks to the baby.
Breast-feeding: Butorphanol has been found in breast milk after nursing mothers are given Butorphanol Tartrate Injection. However, the amount passed to the infant is likely too small to cause harm (about 4 mcg per liter of milk if the mother is receiving 2 mg IM four times a day). When deciding whether to use this medication while breastfeeding, the benefits of breastfeeding should be weighed against the mother's need for the medication and any potential risks to the baby, either from the drug itself or from the condition of the mother.
Infants who are exposed to Butorphanol Tartrate Injection through breast milk should be closely monitored for signs of excessive drowsiness and difficulty breathing. Withdrawal symptoms may occur in breastfed infants when the mother stops taking the opioid pain medication or when breastfeeding is discontinued.

The following adverse experiences were reported at a frequency of 1% or greater in clinical trials and were considered to be probably related to the use of butorphanol: See Table 1.

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The following adverse experiences were reported with a frequency of less than 1% in clinical trials and were considered to be probably related to the use of butorphanol: See Table 2.

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The following infrequent additional adverse experiences were reported in a frequency of less than 1% of the patients studied in trials of Butorphanol Tartrate Injection and under circumstances where the association between these events and butorphanol administration is unknown. They are being listed as alerting information for the physician due to their clinical significance. (See Table 3.)

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Benzodiazepines and Other Central Nervous System (CNS) Depressants: The concomitant use of Butorphanol Tartrate Injection with benzodiazepines or other CNS depressants - such as alcohol, sedatives, hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, or other opioids - can lead to additive effects. This significantly increases the risk of low blood pressure, respiratory depression, excessive sedation, coma, and even death.
These drugs should only be prescribed together when other treatment options are not effective or appropriate. Use the lowest effective dose for the shortest possible time, and monitor patients closely for signs of breathing problems and excessive drowsiness.
Serotonergic Drugs: Concomitant use of opioids, including butorphanol, with medications that affect the serotonergic system - such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 antagonists, serotonin-active agents (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (e.g., cyclobenzaprine, metaxalone), and monoamine oxidase inhibitors (MAOIs, including linezolid and IV methylene blue) - may increase the risk of serotonin syndrome.
If concurrent use is necessary, closely monitor patients, especially during treatment initiation and dose adjustments. Discontinue Butorphanol Tartrate Injection immediately if serotonin syndrome is suspected.
Cytochrome P450 (CYP450) Interactions: It is currently unknown whether the effects of Butorphanol Tartrate Injection are altered by medications that influence liver enzymes responsible for drug metabolism (CYP450 inhibitors or inducers), such as erythromycin or theophylline. Clinicians should remain cautious and consider initiating treatment with a lower dose and increasing the dosing interval when such drugs are used concurrently.
Monoamine Oxidase Inhibitors (MAOIs): There is no available data regarding the concurrent use of butorphanol with MAOIs. Patients should be advised to avoid using these medications together.

Store at temperatures not exceeding 30°C.
Shelf-Life: 36 months.

Analgesics (Opioid)

N02AF01 - butorphanol ; Belongs to the class of morphinan derivative opioids. Used to relieve pain.

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