Fluothane

Fluothane® (halothane, USP) is available in unit packages of 125 mL (NDC 0046-3125-81) and 250 mL (NDC 0046-3125-82) of halothane, USP, stabilized with 0.01% thymol (w/w) and up to 0.00025% ammonia (w/w).

HANDLING AND STORAGE

Store at room temperature (approximately 25°C) in a tight, closed container.

Protect from light.

Use carton to protect contents from light.

PHYSICIAN REFERENCE

1. Gregory, GA et al: Anesthesiology 1969; 30 ( 5  ):488-491.

Manufactured for:  
Ayerst Laboratories Inc.
A Wyeth-Ayerst Company
Philadelphia, PA 19101
By ICI Chemicals and Polymers Ltd.
Runcorn, Cheshire, U.K.

Fluothane (halothane, USP) is indicated for the induction and maintenance of general anesthesia.

Fluothane (halothane) may be administered by the nonrebreathing technique, partial rebreathing, or closed technique. The induction dose varies from patient to patient but is usually within the range of 0.5% to 3%. The maintenance dose varies from 0.5% to 1.5%.

Fluothane (halothane) may be administered with either oxygen or a mixture of oxygen and nitrous oxide.

Fluothane (halothane) should not be kept indefinitely in vaporizer bottles not specifically designed for its use. Thymol does not volatilize along with Fluothane (halothane) and, therefore, accumulates in the vaporizer and may, in time, impart a yellow color to the remaining liquid or to wicks in vaporizers. The development of such discoloration may be used as an indicator that the vaporizer should be drained and cleaned, and the discolored Fluothane (halothane, USP) discarded. Accumulation of thymol may be removed by washing with diethyl ether. After cleaning a wick or vaporizer, make certain all the diethyl ether has been removed before reusing the equipment to avoid introducing ether into the system.

Because of the more rapid uptake of Fluothane (halothane) and the increased blood concentration required for anesthesia in younger patients, the minimum alveolar concentration (MAC) ¹ values will decrease with age as follows:

Fluothane (halothane) is not recommended for obstetrical anesthesia except when uterine relaxation is required.

WARNINGS

When previous exposure to Fluothane (halothane) was followed by unexplained hepatic dysfunction and/or jaundice, consideration should be given to the use of other agents.

PRECAUTIONS

GENERAL

Fluothane (halothane) should be used in vaporizers that permit a reasonable approximation of output, and preferably of the calibrated type. The vaporizer should be placed out of circuit in closed-circuit rebreathing systems; otherwise, overdosage is difficult to avoid. The patient should be closely observed for signs of overdosage, i.e., depression of blood pressure, pulse rate, and ventilation, particularly during assisted or controlled ventilation.

Fluothane (halothane) increases cerebrospinal-fluid pressure. Therefore, in patients with markedly raised intracranial pressure, if Fluothane (halothane) is indicated, administration should be preceded by measures ordinarily used to reduce cerebrospinal-fluid pressure. Ventilation should be carefully assessed, and it may be necessary to assist or control ventilation to ensure adequate oxygenation and carbon dioxide removal.

In susceptible individuals, halothane anesthesia may trigger a skeletal-muscle hypermetabolic state leading to a high oxygen demand and the clinical syndrome known as malignant hyperthermia. The syndrome includes nonspecific features such as muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and unstable blood pressure. (It should also be noted that many of these nonspecific signs may appear with light anesthesia, acute hypoxia, etc.) An increase in overall metabolism may be reflected in an elevated temperature (which may rise rapidly, early or late in the case, but usually is not the first sign of augmented metabolism) and an increased usage of the CO ₂ absorption system (hot canister). PaO ₂ and pH may decrease, and hyperkalemia and a base deficit may appear. Treatment includes discontinuance of triggering agents (e.g., halothane), administration of intravenous dantrolene, and application of supportive therapy. Such therapy includes vigorous efforts to restore body temperature to normal, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base derangements. Renal failure may appear later, and urine flow should be sustained if possible. It should be noted that the syndrome of malignant hyperthermia secondary to halothane appears to be rare.

INFORMATION FOR PATIENTS

When appropriate, as in some cases where discharge is anticipated soon after general anesthesia, patients should be cautioned not to drive automobiles, operate hazardous machinery, or engage in hazardous sports for 24 hours or more (depending on the total dose of Fluothane (halothane) , condition of the patient, and consideration given to other drugs administered after anesthesia).

DRUG INTERACTIONS

Epinephrine or norepinephrine should be employed cautiously, if at all, during Fluothane (halothane, USP) anesthesia, since their simultaneous use may induce ventricular tachycardia or fibrillation.

Nondepolarizing relaxants and ganglionic-blocking agents should be administered cautiously, since their actions are augmented by Fluothane (halothane, USP).

Clinical experience and animal experiments suggest that pancuronium should be given with caution to patients receiving chronic tricyclic antidepressant therapy who are anesthetized with halothane, because severe ventricular arrhythmias may result from such usage.

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY

An 18-month inhalational carcinogenicity study of halothane at 0.05% in the mouse revealed no evidence of anesthetic-related carcinogenicity. This concentration is equivalent to 24 hours of 1% halothane.

Mutagenesis testing of halothane revealed both positive and negative results. In the rat, one-year exposure to trace concentrations of halothane (1 and 10 ppm) and nitrous oxide produced chromosomal damage to spermatogonia cells and bone marrow cells. Negative mutagenesis tests included: Ames bacterial assay, Chinese hamster lung fibroblast assay, sister chromatid exchange in Chinese hamster ovary cells, and human leukocyte culture assay.

Reproduction studies of halothane (10 ppm) and nitrous oxide in the rat caused decreased fertility. This trace concentration corresponds to 1/1000 the human maintenance dose.

PREGNANCY

Teratogenic Effects:   Pregnancy Category C. Some studies have shown Fluothane (halothane) to be teratogenic, embryotoxic, and fetotoxic in the mouse, rat, hamster, and rabbit at subanesthetic and/or anesthetic concentrations. There are no adequate and well-controlled studies in pregnant women. Fluothane (halothane) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

LABOR AND DELIVERY

The uterine relaxation obtained with Fluothane (halothane) , unless carefully controlled, may fail to respond to ergot derivatives and oxytocic posterior pituitary extract.

NURSING MOTHERS

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fluothane (halothane) is administered to a nursing woman.

PEDIATRIC USE

Extensive clinical experience reveals that maintenance concentrations of halothane are generally higher in infants and children, and that maintenance requirements decrease with age. See MAC table, based upon age, in "Dosage and Administration."

SIDE EFFECTS

As with other agents of this type, halothane anaesthesia has been shown to trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia (MH). The syndrome includes non specific features such as hypercapnia, muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias and unstable blood pressure. An increase in overall metabolism may be reflected in an elevated temperature. Treatment includes discontinuation of triggering agents, administration of intravenous dantrolene sodium and application of supportive therapy.

Cardiac arrhythmias, in particular ventricular arrthymias, have been reported as being very common during FLUOTHANE (halothane) use. Typically these are without clinical consequences. Bradycardia and/or hypotension may occur during FLUOTHANE (halothane) anaesthesia. Hypotension may occur particularly during induction.

Shivering may be observed during recovery from anaesthesia, especially if the patient is in cool surroundings.

Post-operative nausea and vomiting may occur after FLUOTHANE anaesthesia.

Anaesthesia with halothane may be followed by abnormalities of liver function or more rarely liver damage (see Contraindications).

DRUG INTERACTIONS

FLUOTHANE (halothane) augments the action of non-depolarising muscle relaxants and the muscle relaxant effects of aminoglycosides.

FLUOTHANE (halothane) may augment the hypotension caused by the ganglionic-blocking effect of tubocurarine.

Caution should be exercised during the administration of adrenaline to patients anaesthetised with FLUOTHANE (halothane) as arrhythmias may be precipitated. For this reason the dose of adrenaline should be restricted and an antiarrhythmic agent administered as appropriate. Caution should also be applied for other sympathomimetics, and for aminophylline and theophylline and tricyclic antidepressants, which may also precipitate arrhythmias.

As with other agents of this type, halothane anaesthesia has been shown to trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia (MH). The syndrome includes non specific features such as hypercapnia, muscle rigidity, tachycardia, tachypnoea, cyanosis, arrhythmias and unstable blood pressure. An increase in overall metabolism may be reflected in an elevated temperature. Treatment includes discontinuation of triggering agents, administration of intravenous dantrolene sodium and application of supportive therapy.

Cardiac arrhythmias, in particular ventricular arrthymias, have been reported as being very common during FLUOTHANE (halothane) use. Typically these are without clinical consequences. Bradycardia and/or hypotension may occur during FLUOTHANE (halothane) anaesthesia. Hypotension may occur particularly during induction.

Shivering may be observed during recovery from anaesthesia, especially if the patient is in cool surroundings.

Post-operative nausea and vomiting may occur after FLUOTHANE anaesthesia.

Anaesthesia with halothane may be followed by abnormalities of liver function or more rarely liver damage (see Contraindications).

In the event of overdosage, or what may appear to be overdosage, drug administration should be stopped, and assisted or controlled ventilation with pure oxygen initiated.

There is no specific antidote. Treatment should be aimed at maintaining respiratory function (by moving the patient to fresh air or inserting an emergency airway with respiratory support) and cardiovascular function.

Cases of internal ingestion must be treated symptomatically.