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AMPHOTERICIN B

Coccidioidomycosis 球孢子菌感染

a)  The recommended intrathecal dose of amphotericin B for coccidioidal meningitis is 0.1 to 1.5 milligrams per dose at intervals ranging from daily to weekly, starting with a low dose and titrating up until the appearance of patient intolerance (severe vomiting, prostration, or transient dose-related mental status) (Galgiani et al, 2005).

2)  Intrathecal test doses of amphotericin B 0.05 and 0.01 milligram have been administered prior to doses of 0.2 to 0.5 milligram intrathecally 3 to 5 times per week into the lumbar, cisternal, or ventricular cerebrospinal fluid (Mandell et al, 1990). The Ommaya reservoir has been used for administration of amphotericin B into the CNS. The use of 10% D5W with amphotericin and placing the patient in the Trendelenburg position after dosing may decrease complications of intrathecal administration (Alazraki et al, 1974).
3)  A patient with an Aspergillus brain abscess was treated with systemic amphotericin B, flucytosine, and rifampin for 6 months via local injections of amphotericin B administered either through a catheter or an Ommaya reservoir. The intracavitary dose, originally 5 micrograms/day, was increased to 40 micrograms/day. After 3 months, treatment was changed to 40 micrograms every other day and then discontinued after a total of 6 months because injections became difficult as a result of scar tissue formation. Although the recovery was slow and not without complications, the patient did survive (Camarata et al, 1992).

ARTIFICIAL

CEREBROSPINAL FLUID

1)  IMPORTANT NOTE

a)  Individual Drug Evaluation monographs on methotrexate and cytarabine should be consulted for specific intrathecal dosing information in adults.

2)  Artificial cerebrospinal fluid is indicated as a diluent for intrathecal administration methotrexate sodium and cytarabine (Prod Info Elliott's B(R) Solution, 1996a). It may also be used as a diluent for intrathecal hydrocortisone sodium succinate (Cradock et al, 1978b; Cheung et al, 1984b). Artificial cerebrospinal fluid is intended only for intrathecal use (Prod Info Elliott's B(R) Solution, 1996a). Intrathecal injection volumes have not usually exceeded 12 milliliters (Prod Info Methotrexate, 1995)(Prod Info Cytosar-U(R), 1995; AMA Department of Drugs, 1995; Cradock et al, 1978b).
3)  A sterile filter-needle should be employed for withdrawing ampule contents of artificial cerebrospinal fluid (Prod Info Elliott's B(R) Solution, 1996a).
4)  For methotrexate, the dose should be based on age rather than body surface area, as cerebrospinal fluid volume is dependent upon age (Gagliano & Costanzi, 1976; AMA Department of Drugs, 1995). Only preservative-free methotrexate should be used, and the drug should be diluted with artificial cerebrospinal fluid to a concentration of 1 milligram/milliliter; the usual intrathecally injected volume is 12 milliliters in adults (Prod Info Methotrexate, 1995)(AMA Department of Drugs, 1995). Intrathecal doses of cytarabine have varied considerably in adults and children (AMA Department of Drugs, 1995); only preservative-free cytarabine formulations should be used for intrathecal administration (Prod Info Elliott's B(R) Solution, 1996a).
5)  After dilution of methotrexate to 1 or 2.5 mg/mL in artificial cerebrospinal fluid, the pH of the solution was maintained between 7.2 and 7.8 in one study. Methotrexate formulations used were injectable solutions of 2.5 mg/mL or 25 mg/mL, and 50 mg lyophilized powder. With addition of cytarabine (from 100 mg vial) to artificial cerebrospinal fluid (final concentration 2.5 mg/mL), a pH of 7.3 was reported. In contrast, a wider range of pH values was observed after addition of these single drugs to lactated Ringer's or normal saline (overall, 5.3 to 8.5) (Cradock et al, 1978)
6)  In usual doses prepared for clinical use, methotrexate, cytarabine, and hydrocortisone sodium succinate can be mixed together in artificial cerebrospinal fluid, and stability is maintained for at least 10 hours at room temperature. Doses were added to 12 milliliters of solution (12 milligrams methotrexate, 30 to 50 milligrams cytarabine, 15 to 25 milligrams hydrocortisone sodium succinate). After mixing methotrexate 12 mg, cytarabine 30 to 50 mg, plus hydrocortisone sodium succinate 15 to 25 mg together in artificial cerebrospinal fluid (volume of 12 mL), pH values were 7.1 to 7.2. These values were higher than after combined admixture of these drugs in normal saline (pH 6) or lactated Ringer's (pH 6) (Cheung et al, 1984b).
7)  The pH of artificial cerebrospinal fluid has been maintained at approximately 7.3 after addition of hydrocortisone sodium succinate (concentration, 1 or 2.5 mg/mL); with use of lactated Ringer's or normal saline as diluents, the final pH was consistently 7.0 (Cradock et al, 1978).

BACLOFEN  

Intrathecal route

Spasticity

a)  SCREENING PHASE

1)  It is recommended that a single bolus test dose of 50 micrograms (mcg) in 1 mL be administered intrathecally. This test dose is given by barbotage over at least 1 minute, and increased in 25 mcg increments every 24 hours until a 4- to 8-hour positive clinical response is demonstrated. Patients must respond to a single bolus dose of no greater than 100 mcg/2 mL to be acceptable candidates for chronic therapy with the intrathecal infusion pump (Prod Info Lioresal(R) Intrathecal, 1999). Patients not responding to the 100 mcg bolus should not be considered candidates for the implanted pump.

b)  POST-IMPLANT DOSE TITRATION PERIOD

1)  For dosing during the post-implant period, the initial daily dose is double the screening dose administered over a 24-hour period, unless the bolus dose efficacy was maintained for more than an 8-hour period; then the starting daily dose should be the screening dose delivered over a 24-hour period. No dose increases should be given during the first 24 hours. In patients with spinal cord spasticity, after the first 24 hours, the daily dosage may be slowly increased by 10% to 30% increments, but only once every 24 hours (Prod Info Lioresal(R) Intrathecal, 1999). Similarly in patients with spasticity due to a cerebral origin, increases should be made more slowly at a rate of 5% to 15%.

c)  MAINTENANCE THERAPY (Spinal cord spasticity)

1)  The daily dose of intrathecal BACLOFEN may be increased by 10% to 40% (maximum of 40%) during periodic pump refills; also, the daily dose may be reduced by 10% to 20% in patients experiencing adverse effects. Most patients require gradual increases in dose over time to maintain optimal response. Maintenance dosages have ranged from 12 to 2003 micrograms/day (most patients: 300 to 800 micrograms/day) (Prod Info Lioresal(R) Intrathecal, 1999).

d)  MAINTENANCE THERAPY (CEREBRAL ORIGIN SPASTICITY)

1)  The daily dose of intrathecal BACLOFEN may be increased by 5% to 20% (maximum of 20%) during periodic pump refills; also, the daily dose may be reduced by 10% to 20% in patients experiencing adverse effects. Most patients require gradual increases in dose over time to maintain optimal response. Maintenance dosages have ranged from 22 to 1400 micrograms/day (most patients: 90 to 703 micrograms/day) (Prod Info Lioresal(R) Intrathecal, 1999).

CLONIDINE

Postoperative pain; Adjunct

1)  In addition to spinal anesthesia with 15 mg hyperbaric bupivacaine, intrathecal clonidine 75 micrograms (mcg) or 25 mcg combined with intrathecal morphine 250 mcg improve postoperative analgesia for TOTAL KNEE ARTHROPLASTY patients (Sites et al, 2003).
2)  Intrathecal clonidine 1 microgram (mcg/kilogram (kg) plus intrathecal morphine 4 mcg/kg improved postoperative analgesia for CORONARY ARTERY BYPASS GRAFT patients (Lena et al, 2003).

CYTARABINE  

Meningeal leukemia; Treatment and Prophylaxis

a)  Intrathecal cytarabine 5 to 75 milligrams/square meter has been used for meningeal leukemia. The most common dose used has been 30 milligrams/square meter every 4 days until normalization of cerebrospinal fluid followed by 1 additional treatment (Prod Info Cytosar-U(R), 1999b).
b)  A diluent containing benzyl alcohol should not be used for the reconstitution of cytarabine intended for intrathecal use. PRESERVATIVE-FREE normal saline, USP, for injection or autologous spinal fluid have been commonly used (Prod Info Cytosar-U(R), 1999b).

CYTARABINE LIPOSOME  

Intrathecal route  

Malignant meningitis, Lymphomatous

a)  Induction

1)  Administer cytarabine liposome 50 milligrams (mg) intrathecally every 14 days for 2 doses (weeks 1 and 3). Also, administer dexamethasone 4 mg twice daily either orally or intravenously for 5 days beginning on the day of liposomal cytarabine injection (Prod Info DEPOCYT(R) injection, 2003).

b)  Consolidation

1)  Administer cytarabine liposome 50 mg intrathecally every 14 days for 3 doses (weeks 5, 7, and 9) followed by 1 additional dose at week 13. Also, administer dexamethasone 4 mg twice daily either orally or intravenously for 5 days beginning on the day of liposomal cytarabine injection (Prod Info DEPOCYT(R) injection, 2003).

c)  Maintenance

1)  Administer cytarabine liposome 50 mg intrathecally every 28 days for 4 doses (weeks 17, 21, 25, and 29). Also, administer dexamethasone 4 mg twice daily either orally or intravenously for 5 days beginning on the day of liposomal cytarabine injection (Prod Info DEPOCYT(R) injection, 2003).

DIACETYLMORPHINE  

Intrathecal route

1)  Some studies have reported intrathecal administration of diacetylmorphine to be associated with a limiting incidence of adverse side effects and, thus, the intrathecal route was not recommended (Jacobson et al, 1989a; Reay et al, 1989a). However, in another study, intrathecal administration was associated with less nausea and vomiting than epidural administration of an equivalent dose (Hallworth et al, 1999).

DIAZIQUONE  

Neoplasm of nervous system

a)  MENINGEAL MALIGNANCY

1)  Diaziquone has been given in doses of 1 or 2 milligrams (mg) twice weekly, or 0.5 mg/dose every 6 hours for three doses once weekly. Induction therapy was continued for 4 weeks; those patients achieving complete response after 4 weeks were given the same dose regimen every other week for 6 weeks, then monthly. Patients achieving partial response after 4 weeks were given two additional weeks of induction therapy; those with complete response at 6 weeks were treated every other week for 6 weeks, then monthly (Berg et al, 1992b).

GENTAMICIN  

IMPORTANT NOTE

1)  Garamycin(R) intrathecal injection was discontinued in 1995 by Schering Corporation (Prod Info Garamycin(R) Intrathecal, 1995).

b)  Prior to the intrathecal dosage form being discontinued, it was administered at a dose of 4 to 8 milligrams (mg) once a day, mixed with cerebral spinal fluid and infused over 3 to 5 minutes. This dosage form was 2 mg/milliliter without preservatives (Prod Info Garamycin(R) Intrathecal, 1995).

HYDROMORPHONE  

Pain, chronic (Moderate to Severe)

1)  Cancer Pain

a)  Hydromorphone combined with clonidine is effective for treating intractable cancer pain. Using an intrathecal infusion pump, hydromorphone with clonidine was administered to a 48-year-old cancer patient for pain. When the patient became refractory to hydromorphone alone, the clonidine was added which restored analgesia (Coombs et al, 1986).

INTERFERON BETA, NATURAL  

Multiple sclerosis 多發性硬化症

a)  For the treatment of exacerbating-remitting multiple sclerosis, natural human interferon beta has been administered intrathecally at the time of each lumbar puncture in doses of one million units weekly for the first 4 weeks, then once monthly for 5 months (Jacobs et al, 1986; Jacobs et al, 1987a).

IOHEXOL  

Myelogram

a)  Lumbosacral

1)  The usual recommended dose for use in lumbar myelography is 10 to 17 milliliters of iohexol 180 milligrams iodine/milliliter (mgI/mL) or 7 to 12.5 milliliters of iohexol 240 mgI/mL administered by lumbar injection (Prod Info Omnipaque(R), 1996c).

b)  Thoracic

1)  The usual recommended dose for thoracic myelography is 6 to 12.5 milliliters of iohexol 240 milligrams iodine/milliliter (mgI/mL) or 6 to 10 mL of iohexol 300 mgI/mL administered by lumbar or cervical injection (Prod Info Omnipaque(R), 1996c).

c)  Cervical

1)  For cervial myelography given by lumbar injections, the following doses have been used: 6 to 12.5 milliliters of iohexol 240 milligrams iodine/milliliter(mgI/mL) or 6 to 10 mL of iohexol 300 mgI/mL. If iohexol is administered by C1-2 injection, the recommended dose is 7 to 10 mL of iohexol 180 mgI/mL, 6 to 12.5 mL of iohexol 240 mgI/mL, or 4 to 10 mL of iohexol 300 mgI/mL (Prod Info Omnipaque(R), 1996c).

d)  Spinal cord

1)  The usual dose for total columnar myelography (lumbar injection) is 6 to 12.5 milliliters of iohexol 240 milligrams iodine/milliliter(mgI/mL) or 6 to 10 mL of iohexol 300 mgI/mL (Prod Info Omnipaque(R), 1996c).

2)  Iohexol 180 milligrams iodine/milliliter (mgI/mL), iohexol 240 mgI/mL or iohexol 300 mgI/mL is recommended for the examination of the lumbar, thoracic, or cervical regions and are slightly hypertonic to CSF (Prod Info Omnipaque(R), 1996c).
3)  A total dose of 3060 milligrams iodine or a concentration of 300 milligrams iodine/milliliter should not be exceeded in a single myelographic examination (Prod Info Omnipaque(R), 1996c).
4)  To avoid excessive mixing with cerebrospinal fluid (CSF) and consequent dilution of iohexol solution, injection should be made slowly over 1 to 2 minutes (Prod Info Omnipaque(R), 1996c).
1.3.1.A.5   REPEAT PROCEDURES

a)  If repeat examinations are desired, a suitable interval of time between administrations is needed to allow for normal clearance of the drug from the body. An interval of at least 48 hours should be allowed before repeat examination. However, 5 to 7 days is recommended whenever possible (Prod Info Omnipaque(R), 1996c).

IOPAMIDOL  

Intrathecal route

1)  The manufacturer of iopamidol has provided the following dose recommendations for intrathecal iopamidol (Isovue-M(R)) administration (Prod Info Isovue-M(R), 1997):

2)  Following subarachnoid injection, conventional radiography will continue to provide good diagnostic contrast for at least 30 minutes. At about one hour, diagnostic degree of contrast will not usually be available. However, sufficient contrast for CT myelography will be available for several hours. CT myelography following conventional myelography should be deferred for at least four hours to reduce the degree of contrast (Prod Info Isovue-M(R), 1997).
3)  Aspiration of iopamidol is unnecessary following intrathecal administration (Prod Info Isovue-M(R), 1997).
4)  A solution that is approximately isotonic (ISOVUE-M(R) 200) is recommended for examination of the lumbar region. For movement of the contrast medium to distant target areas, the more concentrated ISOVUE-M(R) 300 preparation should be used to compensate for dilution of iopamidol with cerebrospinal fluid. A total dose in excess of 4500 mg iodine, and iopamidol formulated to contain more than 300 mg/mL should not be used intrathecally (Prod Info Isovue-M(R), 1997).
5)  Anesthesia is not necessary. Premedication with sedatives or tranquilizers is usually not needed. In patients with a history of seizure activity who are not on anticonvulsant therapy, premedication with barbiturates or phenytoin should be considered (Prod Info Isovue-M(R), 1997).
6)  Lumbar puncture is usually made between L3 and L4; if pathology is suspected at this level, the interspace immediately above or below may be selected. A lateral cervical puncture may also be used (Prod Info Isovue-M(R), 1997).
7)  Rate of injection: To avoid excessive mixing with cerebrospinal fluid and consequent loss of contrast as well as premature cephalad dispersion, injection must be made slowly over one to two minutes; the needle may then be removed (Prod Info Isovue-M(R), 1997).
8)  An interval of at least 48 hours should be allowed before repeat examination; however, whenever possible five to seven days is recommended (Prod Info Isovue-M(R), 1997).
9)  It is desirable that solutions of radiopaque diagnostic agents for intrathecal use be at body temperature when injected. In the event that crystallization of the medium has occurred, place the vial in hot (60 to 100 degrees C) water for about five minutes, then shake gently to obtain a clear solution. Cool to body temperature before use. Discard vial without use if solids persist (Prod Info Isovue-M(R), 1997).

IOPHENDYLATE  

Intrathecal route

1)  The amount of iophendylate used for RADIOGRAPHIC PROCEDURES varies and is dependent on physician preference; however, most examinations are performed using from 3 to 12 milliliters (Prod Info Pantopaque(R), 1986b).

1.3.1.C   ADMINISTRATION TECHNIQUE

1)  Patients should be placed face down on a fitting fluoroscopy table. The head may be turned either way, and the hand and arms should be placed in a position of maximum comfort for the patients and so that they will be able to steady themselves during the examination. A small pillow or inflatable balloon may be placed under the lower portion of the abdomen in order to increase the intraspinous spaces (Prod Info Pantopaque(R), 1986b).
2)  Sterile precautions should be employed as in normal lumbar punctures. After scrubbing the injection site, it is important to swab the area dry. Powder-free, sterile gloves should be worn (Prod Info Pantopaque(R), 1986b). The injection of IOPHENDYLATE should not be carried out until it is certain that the needle is in the subarachnoid space (Prod Info Pantopaque(R), 1986b). The puncture is usually made between the third and fourth lumbar vertebrae; however, if pathology is suspected at this level, the interspace above or below should be selected. The skin and subcutaneous tissue should be anesthetized by infiltration with procaine. The use of an 18-gauge, short, beveled, spinal needle is recommended for the administration of iophendylate. The spinal needle, with solid stylet in place, is introduced into the subarachnoid space. Care must be taken to maintain the needle in the midline and to insert the needle gradually after the ligamentum flavum has been encountered. The stylet is removed after it has been ascertained that the needle is placed in the subarachnoid space and 3 to 12 mL of spinal fluid is removed for analysis if clinically indicated (Prod Info Pantopaque(R), 1986b).
3)  There is a possibility of glass particles entering the product while opening the ampule, therefore iophendylate should be filtered through a sterile filter during aspiration from the ampule. Moderate suction is required for this filtering procedure; excessive suction pressure should be avoided, as the filter may rupture. The syringe containing the filtered iophendylate is attached to the needle through a flexible connecting tube (Prod Info Pantopaque(R), 1986b).
4)  Iophendylate is slowly injected into the subarachnoid space. The contrast agent should flow freely. If marked resistance is encountered, the placement of the needle should be assessed. After iophendylate is injected, the syringe and connecting tube is detached from the needle and the stylet replaced. A sterile gauze dressing should then be placed over the adaptor of the needle and the examination may then be performed (Prod Info Pantopaque(R), 1986b).
5)  Iophendylate should be pooled in the mid lumbar region near the point of the needle. The fluoroscopic table should be manipulated slowly since the contrast medium flows very rapidly. The foot of the table should be lowered gradually and any deviation in the iophendylate column studied carefully by fluoroscopy. Spot radiographs are taken as defects in the column are detected. When the iophendylate has been collected in the terminal sac, the table should be slowly tilted in the opposite direction and the media observed for deviation in its flow toward the head. To prevent the flow of iophendylate into the intracranial subarachnoid space where it may be immobilized or from flowing rapidly over the lumbar curve, which may lead to globulation, the examiners should avoid lowering the head too quickly. If the patient extends his/her neck as the head of the table is slowly lowered, the chance of iophendylate entering the intracranial subarachnoid space will be reduced. These maneuvers may be repeated until a satisfactory examination has been obtained. In order to examine each nerve root adequately, it may be desirable to roll the patient from side to side (Prod Info Pantopaque(R), 1986b).
6)  After radiography, iophendylate should be collected around the tip of the needle under fluoroscopic visualization. Many myelographers prefer to use short beveled needle only for the aspiration of iophendylate. An aspiration cannula may also be used for withdrawing the radiopaque agent. An empty sterile syringe attached to the needle via a flexible connecting tube is used to aspirate the pooled iophendylate. Approximately 98% of iophendylate can be aspirated by using the Chynn(R) aspiration cannula. Due to the similarity of design, the Cuatico(R) aspiration cannula should be equally effective. The amount removed can be identified in the barrel of the syringe where it forms a layer under the spinal fluid. Asking the patient to cough should aid in the collection of iophendylate around the tip of the needle. During the aspiration process, the bevel of the needle should be maintained in the cephalad or caudad direction. Occasionally, it may be necessary to maneuver the radiopaque agent under the tip of the aspiration cannula two to three times by tipping the table under the fluoroscopic visualization for maximum removal (Prod Info Pantopaque(R), 1986b).
7)  The patient may be permitted to move from the fluoroscopic table to a bed; however, the patient should remain flat in bed as much as possible for 24 hours (Prod Info Pantopaque(R), 1986b).

METHADONE  

Intrathecal route

a)  Methadone 2 to 5 milligrams has been administered intrathecally to chronic cancer pain patients (Max et al, 1985a).

METHOTREXATE  

Intrathecal route

Disorder of meninges - Leukemia

1)  It is recommended that a dose of 12 milligrams should be used in adults. Since the intrathecal administration of methotrexate based on the previous standard recommended dose of 12 milligrams/m(2) (maximum dose of 15 milligrams) has resulted in high CSF (cerebral spinal fluid) concentrations and neurotoxicity in adults, this dosing scheme should be abandoned (Prod Info Methotrexate, 2003). Since the CSF volume and turnover may decrease with age, dose reduction may be indicated in elderly patients (Prod Info Methotrexate, 2003).

Important Note

1)  Only preservative-free methotrexate diluted with preservative-free 0.9% Sodium Chloride Injection, USP or other suitable medium to a concentration of 1 milligram/milliliter should be used for intrathecal administration (Prod Info Methotrexate, 2003). A concentration of 2.5 mg/mL diluted with distilled/sterile water has been administered intrathecally (Muriel et al, 1983) or via an Ommaya reservoir (Mehta et al, 1983).

2)  In the treatment of meningeal leukemia, intrathecal (IT) methotrexate 12 milligrams may be administered at intervals of 2 to 5 days. Caution should be exercised as IT methotrexate administered at intervals of less than one week may increase subacute toxicity. IT methotrexate should be given until the cell count of the CSF returns to normal, and then one additional dose. IT methotrexate adds significantly to the systemic methotrexate drug level; therefore, concurrent systemic antileukemic therapy should be appropriately adjusted (Prod Info Methotrexate, 2003).

METRIZAMIDE  

Intrathecal route

1)  Dosage and concentration of metrizamide is dependent upon the area under examination, equipment and technique employed, and on the degree and extent of contrast required (Prod Info Amipaque(R), 1990a).
2)  The following doses are recommended by the manufacturer (Prod Info Amipaque(R), 1990a):

IMPORTANT NOTE

1)  Meticulous intravascular administration technique is required with both ionic and nonionic contrast media, particularly during angiographic procedures, to minimize thromboembolic events. Numbers factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications may contribute to the development of thromboembolic events. Meticulous angiographic techniques are recommended, including close attention to guidewire and catheter manipulation, use of manifold systems and/or 3-way stopcocks, frequent catheter flushing with heparinized solutions, and minimizing the length of the procedure. The use of plastic syringes in place of glass syringes has been reported to decrease, but not eliminate, the likelihood of in vitro clotting (Prod Info Amipaque(R), 1990a).

1.3.1.D   MAXIMUM DOSE

1)  A total dose of 3000 milligrams iodine or a concentration of 300 milligrams iodine/milliliter should not be exceeded for intrathecal injection (Prod Info Amipaque(R), 1990a).
2)  The maximum total dose administered to an adult for peripheral arteriography should not exceed 87.5 grams of iodine (Prod Info Amipaque(R), 1990a).
3)  The maximum total dose administered for intravenous digital arteriography for the head and neck should not exceed 87.5 grams of iodine (Prod Info Amipaque(R), 1990a).

MORPHINE  

Obstetric pain 產科疼痛

1)  Pain control for cesarean section delivery was equally effective with either intrathecal or epidural morphine with ketoprofen (orally or rectally), although 100 micrograms (mcg) intrathecal (IT) morphine was recommended due to a decreased incidence of itching with that dose. Investigators used a combined spinal/epidural technique in which parturients (n=146) received bupivacaine, fentanyl, and either 100 mcg IT morphine (n=49), 200 mcg IT morphine (n=47), or 3 milligrams (mg) of epidural morphine. Pain control was similar in all three groups. The IT 100 group having the lowest incidence of itching. The patients in the IT 100 group needed rescue analgesics more often than the IT 200 group (p less than 0.05). The recommendation of 100 mcg IT morphine is based on the higher value placed on the need to treat side effects versus the need for rescue analgesia (Sarvela et al, 2002).
2)  It has been reported that 1.5 milligrams (mg)/0.15 milliliters intrathecal morphine effectively reduced or abolished the pain of labor. All patients (n=12) reported itching of the mouth, face, eyes, and particularly the nose about 30 minutes after injection. Omitting barbotage reduced side effects. Dosage generally should not exceed 1.5 mg (Scott et al, 1980a).

Pain, chronic

1)  Infumorph(R)

a)  In opioid-naive patients, the recommended dose of continuous intrathecal microinfusion of high-potency morphine solution (10 and 25 milligrams/milliliter (mg/mL)) is 0.2 to 1 mg/day. Limit the area of administration to the lumbar region. In opioid-tolerant patients, the recommended dose of continuous intrathecal microinfusion of high-potency morphine solution (10 and 25 mg/mL) is 1 to 10 mg/day. Limit the area of administration to the lumbar region (Prod Info INFUMORPH(TM) 200, INFUMORPH(TM) 500 epidural, intrathecal solution, 2004).

Pain (Moderate to Severe)

1)  The recommended dose of preservative-free morphine sulfate is 0.2 to 1 milligrams intrathecally into the lumbar area. Repeat dosing is not recommended (Prod Info DURAMORPH(TM) IV, epidural or intrathecal injection, 2005).

Postoperative pain

1)  The recommended dose of preservative-free morphine sulfate is 0.2 to 1 milligrams intrathecally into the lumbar area. Repeat dosing is not recommended (Prod Info DURAMORPH(TM) IV, epidural or intrathecal injection, 2005).
2)  Intrathecal morphine (4 milligrams) was effective for coronary artery bypass graft postoperative analgesia when compared to placebo (n=60). Patients receiving intrathecal morphine needed significantly less intravenous morphine than did patients receiving placebo (p=0.05) (Chaney et al, 1996).
3)  In a survey of 59 adult patients who had undergone major orthopedic procedures (total hip replacement or open knee surgery), the effects of intradural morphine in dosages of 0.625, 1.25, and 2.5 milligrams (mg) administered at induction of anesthesia were evaluated. A significant dose-response for duration of analgesia measured by the time to first requirement of postoperative analgesia was found between 0.625 mg and 1.25 mg doses. Mean time to first postoperative analgesic was approximately 15 hours with the lower 0.625 mg dose as compared to about 23 hours with 1.25 mg. No significant difference in duration was observed between 1.25 and 2.5 mg doses. No dose-response correlations were formed for side effects. The optimal dose therefore appears to be between 0.625 and 1.25 mg (Paterson et al, 1984).

POLYMYXIN B  

Intrathecal route

a)  The recommended dose is 50,000 units intrathecally once daily for 3 to 4 days, then 50,000 units every other day for at least 2 weeks after cerebrospinal fluid cultures are negative and sugar content has returned to normal (Prod Info Polymyxin B for Injection, 2003).
b)  Five hundred thousand units polymyxin B sulfate should be dissolved in 10 milliliters sodium chloride injection to yield 50,000 units/milliliter (Prod Info Polymyxin B for Injection, 2003).

ROPIVACAINE

Local anesthetic intrathecal block - Surgical procedure

a)  SPINAL ANESTHESIA

1)  For spinal anesthesia in patients undergoing lower-limb surgery, 3 milliliters of glucose-free 0.5% or 0.75% ropivacaine has been administered. The duration of analgesia and motor block was longer with 0.75% ropivacaine; motor block was reliable only with this concentration (van Kleef et al, 1994a).

SOMATOSTATIN  

Pain

a)  Cancer pain

1)  Intrathecal somatostatin 250 micrograms initially via bolus injection, followed by an infusion of 10 to 50 micrograms/hour, has been used for analgesia in patients with terminal cancer (Chrubasik et al, 1984).

STREPTOMYCIN  

Intrathecal route

a)  This route is rarely used. Ten milliliters of cerebrospinal fluid is removed and 75 to 100 milligrams of streptomycin is diluted in 10 milliliters of normal saline and injected over 10 minutes (AMA Department of Drugs, 1980a).

SUFENTANIL  

Analgesia in labor, Epidural; Adjunct

1)  Needle direction (cephalad or caudad) made no difference in analgesia or side effects of intrathecal sufentanil for pain of labor, but the specific gravity of the solution relative to that of spinal fluid affected both analgesia and occurrence of pruritus. Pain relief was less with sufentanil 10 micrograms in 10% dextrose (higher specific gravity than spinal fluid) than with sufentanil in normal saline (lower specific gravity than spinal fluid). However, itching after drug injection was greater with the saline preparation. None of the 40 patients experienced vomiting (Ferouz et al, 1997).

General anesthesia

1)  CARDIAC SURGERY

a)  Usual dose, 50 micrograms (preservative-free) (combined with morphine 500 micrograms) (Bettex et al, 2002)
b)  Intrathecal administration of combined sufentanil and morphine with target-controlled infusion (TCI) propofol was deemed superior to standard intravenous dosing, allowing a shorter postoperative duration of intubation, adequate analgesia, and better maximal inspiratory capacity, applied in the setting of FAST-TRACK CARDIAC SURGERY in low-risk patients (Bettex et al, 2002).

EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY

1)  Usual dose, 15 micrograms (mcg) intrathecally (Lau et al, 1999)

SUPEROXIDE DISMUTASE  

Amyotrophic lateral sclerosis 肌萎縮性側索硬化症

1)  Intrathecal administration of human recombinant superoxide dismutase by bolus injection (1, 5, 10, and 20 micrograms (mcg)) or continuous infusion (5 to 10 milligrams (mg)/day for 3 to 6 months) was found to be safe and without obvious adverse effects in patients with amyotrophic lateral sclerosis (Cudkowicz et al, 1997a).

TETANUS IMMUNE GLOBULIN  

Tetanus 破傷風

a)  Tetanus immune globulin 250 international units has been used intrathecally in the treatment of tetanus (Gupta et al, 1980). However, intrathecal administration should not be used because it has not been shown to be significantly superior to the intramuscular route (Abrutyn & Berlin, 1991).
b)  Studies investigating intrathecal administration of tetanus immune globulin in the treatment of tetanus have obtained variable success. Intrathecal tetanus immune globulin appears to be more beneficial in treating less severe tetanus. However, intrathecal administration of tetanus immune globulin is not more effective than intramuscular administration and should not be used (Anon, 1980; Abrutyn & Berlin, 1991).
c)  In one study of 97 patients with mild tetanus, 49 were treated with 250 units of human intrathecal tetanus immune globulin and 48 were treated with 1000 units intramuscularly. Only 3 (6%) of those treated intrathecally worsened, and one (2%) of these died. Thirty-one percent of the intramuscularly treated group worsened, and 10 (21%) died (Gupta et al, 1980).

VANCOMYCIN  

Bacterial meningitis

1)  Intrathecal administration of vancomycin may be considered in patients nonresponsive to parenteral administration. The recommended dose of vancomycin is 5 to 20 milligrams (mg) intrathecally daily. Most studies have used a 10- or 20 mg dose (Tunkel et al, 2004).

b)  A patient was successfully treated for baclofen pump-associated meningitis (Staphylococcus epidermidis) with intrathecal vancomycin after failing intravenous vancomycin therapy at doses of 1000 milligrams (mg) every twelve hours. An 18 milliliter (mL) solution containing 90 mg of vancomycin (1.8 mL), 3330 micrograms (mcg) of baclofen (6.7 mL), and 9.5 mL of normal saline was prepared, with a final concentration of 5 mg/milliliter (mL) vancomycin and 185 micrograms/mL baclofen. This was delivered by intrathecal pump at a rate of 1 mL per day (5 mg/day of vancomycin). Intrathecal gentamicin and oral rifampin were also used during the treatment course. Intravenous vancomycin was continued for the first 3 days of intrathecal therapy. The CSF showed no growth within 2 weeks of therapy, and therapy was continued for a total of 4 weeks (Zed et al, 2000).
c)  In a review by (Luer & Hatton, 1993), initial intraventricular dosing of vancomycin for ventriculitis/shunt infections or meningitis should range from 5 to 10 milligrams/day in infants and 10 to 20 milligrams/day in adults. This is assuming patients have normal ventricular volumes and CSF dynamics with complete CSF drug distribution. Trough CSF concentrations should be 10 to 20 micrograms/mL; the dose or trough may be adjusted based on clinical response and sensitivity data. In addition, intravenous vancomycin is recommended to be administered concurrently with intraventricular therapy. It has been suggested that intraventricular therapy continue for 3 to 4 days after CSF cultures are negative.

ZICONOTIDE  

Intrathecal route
Pain, chronic (Severe), in patients intolerant of or refractory to systemic analgesics, adjunctive therapies, or intrathecal morphine

a)  Intrathecal ziconotide should be initiated at no more than 2.4 micrograms (mcg)/day (0.1 mcg/hour (h)) and titrated to patient response. Doses may be titrated upward by up to 2.4 mcg/day (0.1 mcg/h) at intervals of no more than 2 to 3 times per week, up to a recommended maximum of 19.2 mcg/day (0.8 mcg/h) by day 21. Clinical trials have not assessed use beyond 3 weeks. Adjust dose according to patient's severity of pain, response to therapy and occurrence of adverse events (Prod Info PRIALT(R) intrathecal injection, 2006). .
b)  Doses ranging from 0.3 to 10 micrograms/kilogram/day (mcg/kg) (0.3 mcg/kg/day; 1 mcg/kg/day; 3 mcg/kg/day; 10 mcg/kg/day) by continuous intravenous infusion have been used in healthy males (McGuire et al, 1996a; Luther et al, 1994).

2)  Ziconotide is intended for intrathecal administration using a programmable implanted variable-rate microinfusion device or an external microinfusion device and catheter; it is not intended for intravenous use. Ziconotide may be administered undiluted or diluted with preservative-free 0.9% Sodium Chloride Injection (Prod Info PRIALT(R) intrathecal injection, 2006).
3)  When using the Medtronic SynchroMed EL or SynchroMed II infusion System, only the undiluted 25 micrograms/milliliter (mcg/mL) formulation should be used for naive pump priming and initial pump fill. Rinse the internal surfaces of the pump with 2 mL of 25 mcg/mL solution; repeat twice for a total of 3 rinses. Fill with the appropriate volume of 25 mcg/mL solution and deliver up to a maximum rate of 2.4 mcg/day (0.1 mcg/hour). Refill pump reservoir within 14 days for the first refill; subsequently, refill at least every 40 days for diluted solution or every 84 days for undiluted solution using the Medtronic refill kit. Empty pump contents prior to refilling (Prod Info PRIALT(R) intrathecal injection, 2006).
4)  When using the CADD-Micro ambulatory infusion pump, dilute with preservative-free 0.9% sodium chloride to a concentration of 5 micrograms/milliliter (mcg/mL) to fill the external microinfusion device. Start at a flow rate at 0.02 mL/hour to deliver 2.4 mcg/day (0.1 mcg/hour). Change the dose rate by adjusting the flow rate or concentration (Prod Info PRIALT(R) intrathecal injection, 2006).