Data from FDA (Food and Drug Administration, USA) - Curated by Toby Galbraith - Last updated 09 September 2017

Indication(s)

INDICATIONS AND USAGE MARCAINE Spinal is indicated for the production of subarachnoid block (spinal anesthesia). Standard textbooks should be consulted to determine the accepted procedures and techniques for the administration of spinal anesthesia.

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Advisory information

contraindications
CONTRAINDICATIONS MARCAINE Spinal is contraindicated in patients with a known hypersensitivity to it or to any local anesthetic agent of the amide-type. The following conditions preclude the use of spinal anesthesia: 1.Severe hemorrhage, severe hypotension or shock and arrhythmias, such as complete heart block, which severely restrict cardiac output. 2.Local infection at the site of proposed lumbar puncture. 3.Septicemia.
Special warnings and precautions
PRECAUTIONS General: The safety and effectiveness of spinal anesthetics depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use. (See WARNINGS and ADVERSE REACTIONS .) The patient should have IV fluids running via an indwelling catheter to assure a functioning intravenous pathway. The lowest dosage of local anesthetic that results in effective anesthesia should be used. Aspiration for blood should be performed before injection and injection should be made slowly. Tolerance varies with the status of the patient. Elderly patients and acutely ill patients may require reduced doses. Reduced doses may also be indicated in patients with increased intra-abdominal pressure (including obstetrical patients), if otherwise suitable for spinal anesthesia. There should be careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness after local anesthetic injection. Restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, depression, or drowsiness may be early warning signs of central nervous system toxicity. Spinal anesthetics should be used with caution in patients with severe disturbances of cardiac rhythm, shock, or heart block. Sympathetic blockade occurring during spinal anesthesia may result in peripheral vasodilation and hypotension, the extent depending on the number of dermatomes blocked. Patients over 65 years, particularly those with hypertension, may be at increased risk for experiencing the hypotensive effects of MARCAINE Spinal. Blood pressure should, therefore, be carefully monitored especially in the early phases of anesthesia. Hypotension may be controlled by vasoconstrictors in dosages depending on the severity of hypotension and response of treatment. The level of anesthesia should be carefully monitored because it is not always controllable in spinal techniques. Because amide-type local anesthetics such as MARCAINE are metabolized by the liver, these drugs, especially repeat doses, should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. Local anesthetics should also be used with caution in patients with impaired cardiovascular function because they may be less able to compensate for functional changes associated with the prolongation of AV conduction produced by these drugs. However, dosage recommendations for spinal anesthesia are much lower than dosage recommendations for other major blocks and most experience regarding hepatic and cardiovascular disease dose-related toxicity is derived from these other major blocks. Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine are employed in patients during or following the administration of potent inhalation agents. In deciding whether to use these products concurrently in the same patient, the combined action of both agents upon the myocardium, the concentration and volume of vasoconstrictor used, and the time since injection, when applicable, should be taken into account. Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Because it is not known whether amide-type local anesthetics may trigger this reaction and because the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for management should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures, and dantrolene. (Consult dantrolene sodium intravenous package insert before using.) The following conditions may preclude the use of spinal anesthesia, depending upon the physician's evaluation of the situation and ability to deal with the complications or complaints which may occur: •Pre-existing diseases of the central nervous system, such as those attributable to pernicious anemia, poliomyelitis, syphilis, or tumor. •Hematological disorders predisposing to coagulopathies or patients on anticoagulant therapy. Trauma to a blood vessel during the conduct of spinal anesthesia may, in some instances, result in uncontrollable central nervous system hemorrhage or soft tissue hemorrhage. •Chronic backache and preoperative headache. •Hypotension and hypertension. •Technical problems (persistent paresthesias, persistent bloody tap). •Arthritis or spinal deformity. •Extremes of age. •Psychosis or other causes of poor cooperation by the patient. Information for Patients: When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of spinal anesthesia. Also, when appropriate, the physician should discuss other information including adverse reactions in the MARCAINE Spinal package insert. Clinically Significant Drug Interactions: The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe persistent hypertension or cerebrovascular accidents. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term studies in animals to evaluate the carcinogenic potential of bupivacaine hydrochloride have not been conducted. The mutagenic potential and the effect on fertility of bupivacaine hydrochloride have not been determined. Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. MARCAINE Spinal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Bupivacaine hydrochloride produced developmental toxicity when administered subcutaneously to pregnant rats and rabbits at clinically relevant doses. This does not exclude the use of MARCAINE Spinal at term for obstetrical anesthesia or analgesia. (See Labor and Delivery.) Bupivacaine hydrochloride was administered subcutaneously to rats at doses of 4.4, 13.3, & 40 mg/kg and to rabbits at doses of 1.3, 5.8, & 22.2 mg/kg during the period of organogenesis (implantation to closure of the hard palate). The high doses are approximately 30-times the daily maximum recommended human dose (MRHD) of 12 mg/day on a mg dose/m2 body surface area (BSA) basis. No embryo-fetal effects were observed in rats at the high dose which caused increased maternal lethality. An increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity with the fetal No Observed Adverse Effect Level being approximately 8-times the MRHD on a BSA basis. In a rat pre- and post-natal development study (dosing from implantation through weaning) conducted at subcutaneous doses of 4.4, 13.3, & 40 mg/kg, decreased pup survival was observed at the high dose. The high dose is approximately 30-times the daily MRHD of 12 mg/day on a BSA basis. Labor and Delivery: Spinal anesthesia has a recognized use during labor and delivery. Bupivacaine hydrochloride, when administered properly, via the epidural route in doses 10 to 12 times the amount used in spinal anesthesia has been used for obstetrical analgesia and anesthesia without evidence of adverse effects on the fetus. Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient's legs and positioning her on her left side will help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable. It is extremely important to avoid aortocaval compression by the gravid uterus during administrations of regional block to parturients. To do this, the patient must be maintained in the left lateral decubitus position or a blanket roll or sandbag may be placed beneath the right hip and the gravid uterus displaced to the left. Spinal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Spinal anesthesia has also been reported to prolong the second stage of labor by removing the parturient's reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance. The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. This has not been reported with bupivacaine. There have been reports of cardiac arrest during use of MARCAINE 0.75% solution for epidural anesthesia in obstetrical patients. The package insert for MARCAINE hydrochloride for epidural, nerve block, etc., has a more complete discussion of preparation for, and management of, this problem. These cases are compatible with systemic toxicity following unintended intravascular injection of the much larger doses recommended for epidural anesthesia and have not occurred within the dose range of bupivacaine hydrochloride 0.75% recommended for spinal anesthesia in obstetrics. The 0.75% concentration of MARCAINE is therefore not recommended for obstetrical epidural anesthesia. MARCAINE Spinal (bupivacaine hydrochloride in dextrose injection) is recommended for spinal anesthesia in obstetrics. Nursing Mothers: Bupivacaine has been reported to be excreted in human milk suggesting that the nursing infant could be theoretically exposed to a dose of the drug. Because of the potential for serious adverse reactions in nursing infants from bupivacaine, a decision should be made whether to discontinue nursing or not administer bupivacaine, taking into account the importance of the drug to the mother. Pediatric Use: Until further experience is gained in patients younger than 18 years, administration of MARCAINE Spinal in this age group is not recommended. Geriatric Use: Patients over 65 years, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing spinal anesthesia with MARCAINE Spinal. (See PRECAUTIONS , General and ADVERSE REACTIONS , Cardiovascular System.) Elderly patients may require lower doses of MARCAINE Spinal. (See PRECAUTIONS , General and DOSAGE AND ADMINISTRATION .) In clinical studies, differences in various pharmacokinetic parameters have been observed between elderly and younger patients. (See CLINICAL PHARMACOLOGY , Pharmacokinetics.) This product is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY , Pharmacokinetics.)
Adverse reactions
ADVERSE REACTIONS Reactions to bupivacaine are characteristic of those associated with other amide-type local anesthetics. The most commonly encountered acute adverse experiences which demand immediate countermeasures following the administration of spinal anesthesia are hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia. These may lead to cardiac arrest if untreated. In addition, dose-related convulsions and cardiovascular collapse may result from diminished tolerance, rapid absorption from the injection site, or from unintentional intravascular injection of a local anesthetic solution. Factors influencing plasma protein binding, such as acidosis, systemic diseases which alter protein production, or competition of other drugs for protein binding sites, may diminish individual tolerance. Respiratory System: Respiratory paralysis or underventilation may be noted as a result of upward extension of the level of spinal anesthesia and may lead to secondary hypoxic cardiac arrest if untreated. Preanesthetic medication, intraoperative analgesics and sedatives, as well as surgical manipulation, may contribute to underventilation. This will usually be noted within minutes of the injection of spinal anesthetic solution, but because of differing maximal onset times, differing intercurrent drug usage and differing surgical manipulation, it may occur at any time during surgery or the immediate recovery period. Cardiovascular System: Hypotension due to loss of sympathetic tone is a commonly encountered extension of the clinical pharmacology of spinal anesthesia. This is more commonly observed in elderly patients, particularly those with hypertension, and patients with shrunken blood volume, shrunken interstitial fluid volume, cephalad spread of the local anesthetic, and/or mechanical obstruction of venous return. Nausea and vomiting are frequently associated with hypotensive episodes following the administration of spinal anesthesia. High doses, or inadvertent intravascular injection, may lead to high plasma levels and related depression of the myocardium, decreased cardiac output, bradycardia, heart block, ventricular arrhythmias, and, possibly, cardiac arrest. (See WARNINGS , PRECAUTIONS , and OVERDOSAGE sections.) Central Nervous System: Respiratory paralysis or underventilation secondary to cephalad spread of the level of spinal anesthesia (see Respiratory System ) and hypotension for the same reason (see Cardiovascular System ) are the two most commonly encountered central nervous system-related adverse observations which demand immediate countermeasures. High doses or inadvertent intravascular injection may lead to high plasma levels and related central nervous system toxicity characterized by excitement and/or depression. Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Neurologic: The incidences of adverse neurologic reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration, and the physical status of the patient. Many of these effects may be related to local anesthetic techniques, with or without a contribution from the drug. Neurologic effects following spinal anesthesia may include loss of perineal sensation and sexual function; persistent anesthesia, paresthesia, weakness and paralysis of the lower extremities, and loss of sphincter control all of which may have slow, incomplete, or no recovery; hypotension, high or total spinal block; urinary retention; headache; backache; septic meningitis, meningismus; arachnoiditis; slowing of labor; increased incidence of forceps delivery; shivering; cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid; and fecal and urinary incontinence. Allergic: Allergic-type reactions are rare and may occur as a result of sensitivity to the local anesthetic. These reactions are characterized by signs such as urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and, possibly, anaphylactoid-like symptomatology (including severe hypotension). Cross sensitivity among members of the amide-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitely established. Other: Nausea and vomiting may occur during spinal anesthesia.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION The dose of any local anesthetic administered varies with the anesthetic procedure, the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the depth of anesthesia and degree of muscle relaxation required, the duration of anesthesia desired, individual tolerance, and the physical condition of the patient. The smallest dose and concentration required to produce the desired result should be administered. Dosages of MARCAINE Spinal should be reduced for elderly and debilitated patients and patients with cardiac and/or liver disease. For specific techniques and procedures, refer to standard textbooks. There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. MARCAINE Spinal is not approved for this use (see WARNINGS and DOSAGE AND ADMINISTRATION ). The extent and degree of spinal anesthesia depend upon several factors including dosage, specific gravity of the anesthetic solution, volume of solution used, force of injection, level of puncture, and position of the patient during and immediately after injection. Seven and one-half mg (7.5 mg or 1 mL) MARCAINE Spinal has generally proven satisfactory for spinal anesthesia for lower extremity and perineal procedures including TURP and vaginal hysterectomy. Twelve mg (12 mg or 1.6 mL) has been used for lower abdominal procedures such as abdominal hysterectomy, tubal ligation, and appendectomy. These doses are recommended as a guide for use in the average adult and may be reduced for the elderly or debilitated patients. Because experience with MARCAINE Spinal is limited in patients below the age of 18 years, dosage recommendations in this age group cannot be made. Obstetrical Use: Doses as low as 6 mg bupivacaine hydrochloride have been used for vaginal delivery under spinal anesthesia. The dose range of 7.5 mg to 10.5 mg (1 mL to 1.4 mL) bupivacaine hydrochloride has been used for Cesarean section under spinal anesthesia. In recommended doses, MARCAINE Spinal produces complete motor and sensory block. Unused portions of solutions should be discarded following initial use. MARCAINE Spinal should be inspected visually for discoloration and particulate matter prior to administration; solutions which are discolored or which contain particulate matter should not be administered.
Pregnancy and lactation
Nursing Mothers: Bupivacaine has been reported to be excreted in human milk suggesting that the nursing infant could be theoretically exposed to a dose of the drug. Because of the potential for serious adverse reactions in nursing infants from bupivacaine, a decision should be made whether to discontinue nursing or not administer bupivacaine, taking into account the importance of the drug to the mother.

Interactions

Clinically Significant Drug Interactions: The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs and of ergot-type oxytocic drugs may cause severe persistent hypertension or cerebrovascular accidents. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.

More information

Category Value
Authorisation number NDA018692
Agency product number 7TQO7W3VT8
Orphan designation No
Product NDC 0409-1761
Date Last Revised 24-05-2017
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder Hospira, Inc.