(Revised 5/19/97 - Isoniazid)
Note: The following summaries include only those safety-related sections that have been modified, and therefore do not contain all the information needed for safe and effective prescribing. Contact the manufacturer for the complete labeling/package insert.
NB: Comparison made to 1996 Physicians' Desk Reference (PDR), if drug's labeling included in the PDR.
ASACOL
[Aug 29, 1996: Procter & Gamble]
AZACTAM
[Aug 20, 1996: Bristol Myers Squibb]
BSS PLUS
[Aug 14, 1996: Alcon]
CATAPRES
[Aug 2, 1996: Boehringer Ingelheim]
CIPRO IV
0.2% solution in 5% dextrose
and 0.2% solution in 0.9% sodium chloride
[Aug 9, 1996: Bayer]
CYSTAGON
[Aug 16, 1996: Mylan]
DDAVP
[Aug 7, 1996: Rhone-Poulenc Rorer]
DIFLUCAN
[Aug 6, 1996: Pfizer]
DOVONEX
[Aug 15, 1996: Westwood-Squibb]
HUMATROPE
[Aug 5, 1996: Eli Lilly]
IOPIDINE
Ophthalmic Solution, 1%
[Aug 27, 1996: Procter & Gamble]
ISONIAZID
[Aug 1, 1996: Eon]
"Therefore, patients given isoniazid should be carefully monitored and interviewed at monthly intervals. For persons 35 and older, in addition to monthly symptom reviews, hepatic enzymes (specifically, AST and ALT (formerly SGOT and SGPT, respectively)) should be measured prior to starting isoniazid therapy and periodically throughout treatment. Isoniazid- associated hepatitis usually occurs during the first three months of treatment. (replaces "Serum transaminase concentration becomes elevated in about 10-20 percent of patients, usually during the first few months of therapy but it can occur at any time.") Usually, enzyme levels return to normal despite continuance of drug, but in some cases progressive liver dysfunction occurs. Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease and injection drug use. A recent report suggests an increased risk of fatal hepatitis associated with isoniazid amoung women, particularly black and Hispanic women. The risk may also be increased during the post partum period. More careful monitoring should be considered in these groups, possibly including more frequent laboratory monitoring. If abnormalities of liver function exceed three to five times the upper limit of normal, discontinuation of isoniazid should be strongly considered. Liver function tests are not a substitute for a clinical evaluation at monthly intervals or for the prompt assessment of signs or symptoms of adverse reactions occurring between regularly scheduled evaluations. Patients should be instructed to immediately report signs or symptoms consistent with liver damage or other adverse effects. (replaces "report immediately any of the prodromal symptoms of hepatitis, such as"). These include any of the following: unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness (", malaise" deleted) or fever of greater than 3 days duration and/or abdominal tenderness, especially right upper quadrant discomfort. If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since (replaces "sine") continued use of the drug in these cases has been reported to cause a more severe form of liver damage.
"Patients with tuberculosis who have hepatitis attributed to isoniazid should be given appropriate treatment with alternative drugs. If isoniazid must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. The drug should be restarted in very small and gradually (replaces "graually") increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement.
"Preventive treatment should be deferred in persons with acute hepatic diseases."
Mechanism of Action (New Subsection):
"Isoniazid is recommended for all forms of tuberculosis in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant antituberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculosis with isoniazid, or any other medication, is inadequate therapy."
General: "All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If isoniazid therapy must be reinstituted, the drug should be given only after symptoms have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent hypersensitivity reaction."
"Use of isoniazid should be carefully monitored in the following:
"Periodic ophthalmologic examinations during isoniazid therapy are recommended when visual symptoms occur." has been deleted. (NB: See below for revision involving PRECAUTION regarding concurrent use of phenytoin).
Laboratory Tests: "Because there is a higher frequency of isoniazid associated hepatitis among certain patient groups, including Age >35, daily users of alcohol, chronic liver disease, injection drug use and women belonging to minority groups, particularly in the post-partum period, transaminase measurements should be obtained prior to starting and monthly during preventative therapy, or more frequently as needed. If any of the values exceed three to five times the upper limit of normal, isoniazid should be temporarily discontinued and consideration given to restarting therapy."
Drug interactions: "Food: Isoniazid should not be administered with food. Studies have shown that the bioavailability of isoniazid is reduced significantly when administered with food.
"Acetaminophen: a report of severe acetaminophen toxicity was reported in a patient receiving Isoniazid. It is believed that the toxicity may have resulted from a previously unrecognized interaction between isoniazid and acetaminophen and a molecular basis for this interaction has been proposed. However, current evidence suggests that isoniazid does induce P-450IIE1, a mixed-function oxidase enzyme that appears to generate the toxic metabolites, in the liver. Furthermore it has been proposed that isoniazid resulted in induction of P-450IIE1 in the patients liver which, in turn, resulted in a greater proportion of the ingested acetaminophen being converted to the toxic metabolites. Studies have demonstrated that pretreatment with isoniazid potentiates acetaminophen hepatotoxicity in rats1,2.
"Carbamazepine: Isoniazid is known to slow the metabolism of carbamazepine and increase its serum levels. Carbamazepine levels should be determined prior to concurrent administration with isoniazid, signs and symptoms of carbamazepine toxicity should be monitored closely, and appropriate dosage adjustment of the anticonvulsant should be made3.
"Ketoconazole: Potential interaction of Ketoconazole and Isoniazid may exist. When Ketoconazole is given in combination with isoniazid and rifampin the AUC of ketoconazole is decreased by as much as 88% after 5 months of concurrent Isoniazid and Rifampin therapy4.
Phenytoin: NB: Prior labeling contained the following PRECAUTION regarding concurrent use of phenytoin: "1. Patients who are receiving phenytoin concurrently. Isoniazid may decrease the excretion of phenytoin or may enhance its effects. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made."
Revised to: "Isoniazid may increase serum levels of phenytoin. To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made5,6."
"Theophylline: A recent study has shown that concomitant administration of isoniazid and theophylline may cause elevated plasma levels of theophylline, and in some instances a slight decrease in the elimination of isoniazid. Since the therapeutic range of theophylline is narrow, theophylline serum levels should be monitored closely, and appropriate dosage adjustments of theophylline should be made7.
"Valproate: A recent case study has shown a possible increase in the plasma level of valproate when co-administered with isoniazid. Plasma valproate concentration should be monitored when isoniazid and valproate are co-administered, and appropriate dosage adjustments of valproate should be made5."
Prior Sections USAGE IN PREGNANCY AND LACTATION and CARCINOGENESIS have been replaced by these new subections:
Carcinogenesis and Mutagenesis: "Isoniazid has been shown (replaces "reported") to induce pulmonary tumors in a number of strains of mice. Isoniazid has not been shown to be carcinogenic in humans. (Note: a diagnosis of mesothelioma in a child with prenatal exposure to isoniazid and no other apparent risk factors has been reported). Isoniazid has been found to be weakly mutagenic in strains TA 100 and TA 1535 of Salmonella typhimurium (Ames assay) without metabolic activation.
Pregnancy: Prior notation regarding animals studies in pregnancy and usage in pregancy: "It has been reported that in both rats and rabbits, isoniazid may exert an embryocidal effect when administered orally during pregnancy, although no isoniazid-related congenital anomalies have been found in reproduction studies in mammalian species (mice, rats, and rabbits). Isoniazid should be prescribed during pregnancy only when therapeutically necessary. The benefit of preventive therapy should be weighed against a possible risk to the fetus. Preventive treatment generally should be started after delivery because of the increased risk of tuberculosis for new mothers."
has been replaced by: "Teratogenic effects: Pregnancy Category C: Isoniazid has been shown to have an embryocidal effect in rats and rabbits when given orally during pregnancy. Isoniazid was not teratogenic in reproduction studies in mice, rats and rabbits. There are no adequate and well-controlled studies in pregnant women. Isoniazid should be used as a treatment for active tuberculosis during pregnancy because the benefit justifies the potential risk to the fetus. The benefit of preventive therapy also should be weighed against a possible risk to the fetus. Preventive therapy generally should be started after delivery to prevent putting the fetus at risk of exposure; the low levels of isoniazid in breast milk do not threaten the neonate. Since isoniazid is known to cross the placental barrier, neonates of isoniazid treated mothers should be carefully observed for any evidence of adverse affects."
Nonteratogenic effects: Prior statement revised - "Since isoniazid is known to cross the placental barrier ("and to pass into maternal breast milk" deleted), neonates ("and breast-fed infants" deleted) of isoniazid-treated mothers should be carefully observed for any evidence of adverse effects."
Nursing Mothers: "The small concentrations of isoniazid in breast milk do not produce toxicity in the nursing newborn; therefore, breast feeding should not be discouraged. However, because levels of isoniazid are so low in breast milk, they can not be relied upon for prophylaxis or therapy of nursing infants."
In addition, the section has been revised to include separate subsections that specifically outline the management of overdosage in the Asymptomatic Patient and Symptomatic Patient; provide General information as to which blood samples to obtain; discuss the Rapid Control of Metabolic Acidosis; and discuss Dialysis [see complete section in package insert].
"The above treatment guidelines apply only when the disease is caused by organisms that are susceptible to the standard antituberculous agents. Because of the impact of resistance to isoniazid and rifampin on the response to therapy, it is essential that physicians initiating therapy for tuberculosis be familiar with the prevalence of drug resistance in their communities. It is suggested that ethambutol not be used in children whose visual acuity cannot be monitored."
"Pregnant Women with Tuberculosis: The options listed above must be adjusted for the pregnant patient. Streptomycin interferes with in utero development of the ear and may cause congenital deafness. Routine use of pyrazinamide is also not recommended in pregnancy because of inadequate teratogenicity data. The initial treatment regimen should consist of isoniazid and rifampin. Ethambutol should be included unless primary isoniazid resistance is unlikely (isoniazid resistance rate documented to be less than 4%)."
PENTAM 300
[Aug 27, 1996: Fujisawa]
SYSTEM: | EVENT: | % | (previous %) |
---|---|---|---|
Cardiovascular | Hypotension | 5 | (4) |
Hematologic | Leukopenia | 10.4 | (7.5) |
Thrombocytopenia | 2.6 | (0.9) | |
Metabolic | Hypoglycemia | 5.9 | (3.5) |
Urogenital | Azotemia | 8.5 | |
Elevated serum creatine | 23.6 | (23.1) | |
Elevated BUN | 6.6 | ||
Impaired renal function | 28.8 |
PRILOSEC
[Aug 9, 1996: Astra Merck]
PROSCAR
[Aug 28, 1996: Merck]