Isoprodian

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Isoprodian uses

Isoprodian consists of Dapsone, Isoniazid, Protionamide.

Dapsone:


DESCRIPTION

Dapsone-USP, 4,4'-diaminodiphenylsulfone (DDS), is a primary treatment for Dermatitis herpetiformis. It is an antibacterial drug for susceptible cases of leprosy. It is a white, odorless crystalline powder, practically in-soluble in water and insoluble in fixed and vegetable oils.

Isoprodian (Dapsone) is issued on prescription in tablets of 25 and 100 mg for oral use.

Inactive Ingredients: Colloidal silicone dioxide, magnesium stearate, microcrystalline cellulose and corn starch.

Figure

CLINICAL PHARMACOLOGY

Actions: The mechanism of action in Dermatitis herpetiformis has not been established. By the kinetic method in mice, Isoprodian (Dapsone) is bactericidal as well as bacteriostatic against Mycobacterium leprae.

Absorption and Excretion: Isoprodian (Dapsone), when given orally, is rapidly and almost completely absorbed. About 85 percent of the daily intake is recoverable from the urine mainly in the form of water-soluble metabolites. Excretion of the drug is slow and a constant blood level can be maintained with the usual dosage.

Blood Levels: Detected a few minutes after ingestion, the drug reaches peak concentration in 4-8 hours. Daily administration for at least eight days is necessary to achieve a plateau level. With doses of 200 mg daily, this level averaged 2.3 μg/ml with a range of 0.1-7.0 μg/ml. The half-life in the plasma in different individuals varies from ten hours to fifty hours and averages twenty-eight hours. Repeat tests in the same individual are constant. Daily administration (50 - 100 mg) in leprosy patients will provide blood levels in excess of the usual minimum inhibitory concentration even for patients with a short Isoprodian (Dapsone) half-life.

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INDICATIONS AND USAGE

Dermatitis herpetiformis: (D.H.)

Leprosy: All forms of leprosy except for cases of proven Isoprodian (Dapsone) resistance.

CONTRAINDICATION

Hypersensitivity to Isoprodian (Dapsone) and/or its derivatives.

WARNINGS

The patient should be warned to respond to the presence of clinical signs such as sore throat, fever, pallor, purpura or jaundice. Deaths associated with the administration of Isoprodian (Dapsone) have been reported from agranulocytosis, aplastic anemia and other blood dyscrasias. Complete blood counts should be done frequently in patients receiving Isoprodian (Dapsone). The FDA Dermatology Advisory Committee recommended that, when feasible, counts should be done weekly for the first month, monthly for six months and semi-annually thereafter. If a significant reduction in leucocytes, platelets or hemopoiesis is noted, Isoprodian (Dapsone) should be discontinued and the patient followed intensively. Folic acid antagonists have similar effects and may increase the incidence of hematologic reactions; if co-administered with Isoprodian (Dapsone) the patient should be monitored more frequently. Patients on weekly pyrimethamine and Isoprodian (Dapsone) have developed agranulocytosis during the second and third month of therapy.

Severe anemia should be treated prior to initiation of therapy and hemoglobin monitored. Hemolysis and methemoglobin may be poorly tolerated by patients with severe cardiopulmonary disease.

Cutaneous reactions, especially bullous, include exfoliative dermatitis and are probably one of the most serious, though rare, complications of sulfone therapy. They are directly due to drug sensitization. Such reactions include toxic erythema, erythema multiforme, toxic epidermal necrolysis, morbilliform and scarlatiniform reactions, urticaria and erythema nodosum. If new or toxic dermatologic reactions occur, sulfone therapy must be promptly discontinued and appropriate therapy instituted. Leprosy reactional states, including cutaneous, are not hypersensitivity reactions to Isoprodian (Dapsone) and do not require discontinuation. See special section.

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PRECAUTIONS

General: Hemolysis and Heinz body formation may be exaggerated in individuals with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, or methemoglobin reductase deficiency, or hemoglobin M. This reaction is frequently dose-related. Isoprodian (Dapsone) should be given with caution to these patients or if the patient is exposed to other agents or conditions such as infection or diabetic ketosis capable of producing hemolysis. Drugs or chemicals which have produced significant hemolysis in G6PD or methemoglobin reductase deficient patients include Isoprodian (Dapsone), sulfanilamide, nitrite, aniline, phenylhydrazine, napthalene, niridazole, nitro-furantoin and 8-amino-antimalarials such as primaquine.

Toxic hepatitis and cholestatic jaundice have been reported early in therapy. Hyperbilirubinemia may occur more often in G6PD deficient patients. When feasible, baseline and subsequent monitoring of liver function is recommended; if abnormal, Isoprodian (Dapsone) should be discontinued until the source of the abnormality is established.

Drug Interactions: Rifampin lowers Isoprodian (Dapsone) levels 7 to 10-fold by accelerating plasma clearance; in leprosy this reduction has not required a change in dosage. Folic acid antagonists such as pyrimethamine may increase the likelihood of hematologic reactions.

A modest interaction has been reported for patients receiving 100 mg Isoprodian (Dapsone) daily in combination with trimethoprim 5 mg/kg q6h. On Day 7, the serum Isoprodian (Dapsone) levels averaged 2.1 ± 1.0 μg/mL in comparison to 1.5 ± 0.5 μg/mL for Isoprodian (Dapsone) alone. On Day 7, trimethoprim levels averaged 18.4 ± 5.2 μg/mL in comparison to 12.4 ± 4.5 μg/mL for patients not receiving Isoprodian (Dapsone). Thus, there is a mutual interaction between Isoprodian (Dapsone) and trimethoprim in which each raises the level of the other about 1.5 times.

A crossover study1 designed to assess the potential of a drug interaction between Isoprodian (Dapsone), 100 mg/day and trimethoprim, 200 mg every 12 hours, in eight asymptomatic HIV positive volunteers (average CD4 count 524 cells/mm3) demonstrated that there was not a significant drug intreraction between Isoprodian (Dapsone) and trimethoprim. However, an earlier report2 also by Lee et al, in 78 HIV infected patients with acute Pneumocystis carinii pneumonia, receiving Isoprodian (Dapsone), 100 mg/day and higher trimethoprim dose, 20 mg/kg/day, demonstrated that the serum levels of Isoprodian (Dapsone) were increased by 40% and trimethoprim levels were increased by 48% when the drugs were administered concurrently.

Carcinogenesis, mutagenesis: Isoprodian (Dapsone) has been found carcinogenic (sarcomagenic) for male rats and female mice causing mesenchymal tumors in the spleen and peritoneum, and thyroid carcinoma in female rats. Isoprodian (Dapsone) is not mutagenic with or without microsomal activation in S. typhimurium tester strains 1535, 1537, 1538, 98, or 100.

Pregnancy: Teratogenic Effects. Pregnancy Category C: Animal reproduction studies have not been conducted with Isoprodian (Dapsone). Extensive, but uncontrolled experience and two published surveys on the use of Isoprodian (Dapsone) in pregnant women have not shown that Isoprodian (Dapsone) increases the risk of fetal abnormalities if administered during all trimesters of pregnancy or can affect reproduction capacity. Because of the lack of animal studies or controlled human experience, Isoprodian (Dapsone) should be given to a pregnant woman only if clearly needed. In general, for leprosy, USPHS at Carville recommends maintenance of Isoprodian (Dapsone). Isoprodian (Dapsone) has been important for the management of some pregnant D.H. patients.

Nursing Mothers: Isoprodian (Dapsone) is excreted in breast milk in substantial amounts. Hemolytic reactions can occur in neonates. See section on hemolysis. Because of the potential for tumorgenicity shown for Isoprodian (Dapsone) in animal studies a decision should be made whether to discontinue nursing or discontinue the drug taking into account the importance of drug to the mother.

Pediatric Use: Pediatric patients are treated on the same schedule as adults but with correspondingly smaller doses. Isoprodian (Dapsone) is generally not considered to have an effect on the later growth, development and functional development of the pediatric patient.

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ADVERSE REACTIONS

In addition to the warnings listed above, the following syndromes and serious reactions have been reported in patients on Isoprodian (Dapsone).

Hematologic Effects: Dose-related hemolysis is the most common adverse effect and is seen in patients with or without G6PD deficiency. Almost all patients demonstrate the inter-related changes of a loss of 1-2g of hemoglobin, an increase in the reticulocytes (2-12%), a shortened red cell life span and a rise in methemoglobin. G6PD deficient patients have greater responses.

Nervous System Effects: Peripheral neuropathy is a definite but unusual complication of Isoprodian (Dapsone) therapy in non-leprosy patients. Motor loss is predominant. If muscle weakness appears, Isoprodian (Dapsone) should be withdrawn. Recovery on withdrawal is usually substantially complete. The mechanism of recovery is reported by axonal regeneration. Some recovered patients have tolerated retreatment at reduced dosage. In leprosy this complication may be difficult to distinguish from a leprosy reactional state.

Body As A Whole: In addition to the warnings and adverse effects reported above, additional adverse reactions include: nausea, vomiting, abdominal pains, pancreatitis, vertigo, blurred vision, tinnitus, insomnia, fever, headache, psychosis, phototoxicity, pulmonary eosinophilia, tachycardia, albuminuria, the nephrotic syndrome, hypoalbuminemia without proteinuria, renal papillary necrosis, male infertility, drug-induced Lupus erythematosus and an infectious mononucleosis-like syndrome. In general, with the exception of the complications of severe anoxia from overdosage (retinal and optic nerve damage, etc.) these adverse reactions have regressed off drug.

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OVERDOSAGE

Nausea, vomiting, hyperexcitability can appear a few minutes up to 24 hours after ingestion of an overdosage. Methemoglobin induced depression, convulsions or severe cyanosis requires prompt treatment. In normal and methemoglobin reductase deficient patients, methylene blue, 1-2 mg/kg of body weight, given slowly intravenously, is the treatment of choice. The effect is complete in 30 minutes, but may have to be repeated if methemoglobin reaccumulates. For non-emergencies, if treatment is needed, methylene blue may be given orally in doses of 3-5 mg/kg every 4-6 hours. Methylene blue reduction depends on G6PD and should not be given to fully expressed G6PD deficient patients.

DOSAGE AND ADMINISTRATION

Dermatitis herpetiformis: The dosage should be individually titrated starting in adults with 50 mg daily and correspondingly smaller doses in children. If full control is not achieved within the range of 50-300 mg daily, higher doses may be tried. Dosage should be reduced to a minimum maintenance level as soon as possible. In responsive patients there is a prompt reduction in pruritus followed by clearance of skin lesions. There is no effect on the gastrointestinal component of the disease. Isoprodian (Dapsone) levels are influenced by acetylation rates. Patients with high acetylation rates, or who are receiving treatment affecting acetylation may require an adjustment in dosage.

A strict gluten free diet is an option for the patient to elect, permitting many to reduce or eliminate the need for Isoprodian (Dapsone); the average time for dosage reduction is 8 months with a range of 4 months to 2 1/2 years and for dosage elimination 29 months with a range of 6 months to 9 years.

Leprosy: In order to reduce secondary Isoprodian (Dapsone) resistance, the WHO Expert Committee on Leprosy and the USPHS at Carville, LA, recommended that Isoprodian (Dapsone) should be commenced in combination with one or more anti-leprosy drugs. In the multidrug program Isoprodian (Dapsone) should be maintained at the full dosage of 100 mg daily without interruption (with corresponding smaller doses for children) and provided to all patients who have sensitive organisms with new or recrudescent disease or who have not yet completed a two year course of Isoprodian (Dapsone) monotherapy. For advice and other drugs, the USPHS at Carville, LA (1-800-642-2477) should be contacted. Before using other drugs consult appropriate product labeling.

In bacteriologically negative tuberculoid and indeterminate disease, the recommendation is the coadministration of Isoprodian (Dapsone) 100 mg daily with six months of Rifampin 600 mg daily. Under WHO, daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. The Isoprodian (Dapsone) is continued until all signs of clinical activity are controlled - usually after an additional six months. Then Isoprodian (Dapsone) should be continued for an additional three years for tuberculoid and indeterminate patients and for five years for borderline tuberculoid patients.

In lepromatous and borderline lepromatous patients, the recommendation is the co-administration of Isoprodian (Dapsone) 100 mg daily with two years of Rifampin 600 mg daily. Under WHO daily Rifampin may be replaced by 600 mg Rifampin monthly, if supervised. One may elect the concurrent administration of a third anti-leprosy drug, usually either Clofazamine 50-100 mg daily or Ethionamide 250-500 mg daily. Isoprodian (Dapsone) 100 mg daily is continued 3-10 years until all signs of clinical activity are controlled with skin scrapings and biopsies negative for one year. Isoprodian (Dapsone) should then be continued for an additional 10 years for borderline patients and for life for lepromatous patients.

Secondary Isoprodian (Dapsone) resistance should be suspected whenever a lepromatous or borderline lepromatous patient receiving Isoprodian (Dapsone) treatment relapses clinically and bacteriologically, solid staining bacilli being found in the smears taken from the new active lesions. If such cases show no response to regular and supervised Isoprodian (Dapsone) therapy within three to six months or good compliance for the past 3-6 months can be assured, Isoprodian (Dapsone) resistance should be considered confirmed clinically. Determination of drug sensitivity using the mouse footpad method is recommended and, after prior arrangement, is available without charge from the USPHS, Carville, LA. Patients with proven Isoprodian (Dapsone) resistance should be treated with other drugs.

LEPROSY REACTIONAL STATES

Abrupt changes in clinical activity occur in leprosy with any effective treatment and are known as reactional states. The majority can be classified into two groups. The “Reversal” reaction (Type 1) may occur in borderline or tuberculoid leprosy patients often soon after chemotherapy is started. The mechanism is presumed to result from a reduction in the antigenic load: the patient is able to mount an enhanced delayed hypersensitivity response to residual infection leading to swelling (“Reversal”) of existing skin and nerve lesions. If severe, or if neuritis is present, large doses of steroids should always be used. If severe, the patient should be hospitalized. In general anti-leprosy treatment is continued and therapy to suppress the reaction is indicated such as analgesics, steroids, or surgical decompression of swollen nerve trunks. USPHS at Carville, LA should be contacted for advice in management.

Erythema nodosum leprosum (ENL) (lepromatous reaction) (Type 2 reaction) occurs mainly in lepromatous patients and small numbers of borderline patients. Approximately 50% of treated patients show this reaction in the first year. The principal clinical features are fever and tender erythematous skin nodules sometimes associated with malaise, neuritis, orchitis, albuminuria, joint swelling, iritis, epistaxis or depression. Skin lesions can become pustular and/or ulcerate. Histologically there is a vasculitis with an intense polymorphonuclear infiltrate. Elevated circulating immune complexes are considered to be the mechanism of reaction. If severe, patients should be hospitalized. In general, anti-leprosy treatment is continued. Analgesics, steroids, and other agents available from USPHS, Carville, LA, are used to suppress the reaction.

HOW SUPPLIED

Isoprodian (Dapsone) Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15). The blisters are light and child-resistant. NDC 49938-102-30.

Isoprodian (Dapsone) Tablets USP, 100 mg are available as round white scored tablets, debossed “100” above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 30 tablets (2 x 15).The blisters are light and child-resistant. NDC 49938-101-30.

Isoprodian (Dapsone) Tablets USP, 25 mg are available as round white scored tablets, debossed “25” above and “102” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-102-28.

Isoprodian (Dapsone) Tablets USP, 100 mg are available as round white scored tablets, debossed“100" above and “101” below the score and on the obverse “JACOBUS” in a Unit of Use carton of 28 tablets (2 x 14). The blisters are light and child-resistant. NDC 49938-101-28.

REFERENCES

  • Lee, B., et al., Zidovudine, Trimethoprim, and Isoprodian (Dapsone) Pharmacokinetic Interactions in Patients with HIV Infection. Antimicrobial Agents and Chemotherapy, May 1996; 1231-1236.
  • Lee, B., et al., Isoprodian (Dapsone), Trimethoprim, and Sulfamethoxazole Plasma Levels During Treatment of Pneumocystis Carinii Pneumonia in Patients with AIDS, Annals of Internal Medicine, 1989; 110:606-611.

Store at 20°- 25° C (68°- 77°F).. Protect from light.

Rx only. Keep this and all medication out of the reach of children.

JACOBUS PHARMACEUTICAL CO., INC.

P.O. Box 5290

Princeton, NJ 08540

Revised August 2009

0826A09

Principal Display Panel – 25 mg Carton Label

NDC 49938-102-30

Isoprodian (Dapsone)

Tablets USP

25 mg

30 Tablets (2 x 15 unit of use)

Rx Only

To be sold as a single unit

Principal Display Panel – 100 mg Carton Label

NDC 49938-101-30

Isoprodian (Dapsone)

Tablets USP

100 mg

30 Tablets (2 x 15 unit of use)

Rx Only

To be sold as a single unit

Isoniazid:


INDICATIONS AND USAGE

Isoprodian (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 Isoprodian (Isoniazid), or any other medication, is inadequate therapy.

Isoprodian (Isoniazid) is recommended as preventive therapy for the following groups, regardless of age. (Note: the criterion for a positive reaction to a skin test (in millimeters of induration) for each group is given in parenthesis):

  • Persons with human immunodeficiency virus (HIV) infection (≥ 5 mm) and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection.

    Preventive therapy may be considered for HIV infected persons who are tuberculin-negative but belong to groups in which the prevalence of tuberculosis infection is high. Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy.

  • Close contacts of persons with newly diagnosed infectious tuberculosis (≥ 5 mm). In addition, tuberculin-negative (< 5 mm) children and adolescents who have been close contacts of infectious persons within the past 3 months are candidates for preventive therapy until a repeat tuberculin skin test is done 12 weeks after contact with the infectious source. If the repeat skin test is positive (> 5 mm), therapy should be continued.
  • Recent converters, as indicated by a tuberculin skin test (≥ 10 mm increase within a 2-year period for those < 35 years old; ≥ 15 mm increase for those ≥ 35 years of age). All infants and children younger than 4 years of age with a > 10 mm skin test are included in this category.
  • Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis (≥ 5 mm). Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of Isoprodian (Isoniazid) or 4 months of Isoprodian (Isoniazid) and rifampin, concomitantly.
  • Intravenous drug users known to be HIV-seronegative (> 10 mm).
  • Persons with the following medical conditions that have been reported to increase the risk of tuberculosis (≥ 10 mm): silicosis; diabetes mellitus; prolonged therapy with adrenocorticosteroids; immunosuppressive therapy; some hematologic and reticuloendothelial diseases, such as leukemia or Hodgkin's disease; end-stage renal disease; clinical situations associated with substantial rapid weight loss or chronic undernutrition (including: intestinal bypass surgery for obesity, the postgastrectomy state (with or without weight loss), chronic peptic ulcer disease, chronic malabsorption syndromes, and carcinomas of the oropharynx and upper gastrointestinal tract that prevent adequate nutritional intake). Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of Isoprodian (Isoniazid) or 4 months of Isoprodian (Isoniazid) and rifampin, concomitantly.

Additionally, in the absence of any of the above risk factors, persons under the age of 35 with a tuberculin skin test reaction of 10 mm or more are also appropriate candidates for preventive therapy if they are a member of any of the following high-incidence groups:

  • Foreign-born persons from high-prevalence countries who never received BCG vaccine.
  • Medically underserved low-income populations, including high-risk racial or ethnic minority populations, especially blacks, Hispanics, and Native Americans.
  • Residents of facilities for long-term care (e.g., correctional institutions, nursing homes, and mental institutions).

Children who are less than 4 years old are candidates for Isoprodian (Isoniazid) preventive therapy if they have >10 mm induration from a PPD Mantoux tuberculin skin test.

Finally, persons under the age of 35 who a) have none of the above risk factors (1-6); b) belong to none of the high-incidence groups; and c) have a tuberculin skin test reaction of 15 mm or more, are appropriate candidates for preventive therapy.

The risk of hepatitis must be weighed against the risk of tuberculosis in positive tuberculin reactors over the age of 35. However, the use of Isoprodian (Isoniazid) is recommended for those with the additional risk factors listed above (1-6) and on an individual basis in situations where there is likelihood of serious consequences to contacts who may become infected.

CONTRAINDICATIONS

Isoprodian (Isoniazid) is contraindicated in patients who develop severe hypersensitivity reactions, including drug-induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to Isoprodian (Isoniazid) such as drug fever, chills, arthritis; and acute liver disease of any etiology.

WARNINGS

See the boxed WARNING .

PRECAUTIONS

General

All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If Isoprodian 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 Isoprodian (Isoniazid) should be carefully monitored in the following:

  • Daily users of alcohol. Daily ingestion of alcohol may be associated with a higher incidence of + Isoprodian (Isoniazid) hepatitis.
  • Patients with active chronic liver disease or severe renal dysfunction.
  • Age > 35.
  • Concurrent use of any chronically administered medication.
  • History of previous discontinuation of Isoprodian (Isoniazid).
  • Existence of peripheral neuropathy or conditions predisposing to neuropathy.
  • Pregnancy.
  • Injection drug use.
  • Women belonging to minority groups, particularly in the post-partum period.
  • HIV seropositive patients.

Laboratory Tests

Because there is a higher frequency of Isoprodian (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, Isoprodian (Isoniazid) should be temporarily discontinued and consideration given to restarting therapy.

Drug Interactions

Food

Isoprodian should not be administered with food. Studies have shown that the bioavailability of Isoprodian (Isoniazid) is reduced significantly when administered with food. Tyramine- and histamine-containing foods should be avoided in patients receiving Isoprodian (Isoniazid). Because Isoprodian (Isoniazid) has some monoamine oxidase inhibiting activity, an interaction with tyramine-containing foods (cheese, red wine) may occur. Diamine oxidase may also be inhibited, causing exaggerated response (e.g., headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (e.g., skipjack, tuna, other tropical fish).

Acetaminophen

A report of severe acetaminophen toxicity was reported in a patient receiving Isoprodian (Isoniazid). It is believed that the toxicity may have resulted from a previously unrecognized interaction between Isoprodian (Isoniazid) and acetaminophen and a molecular basis for this interaction has been proposed. However, current evidence suggests that Isoprodian (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 Isoprodian (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 Isoprodian (Isoniazid) potentiates acetaminophen hepatotoxicity in rats1,2.

Carbamazepine

Isoprodian is known to slow the metabolism of carbamazepine and increase its serum levels. Carbamazepine levels should be determined prior to concurrent administration with Isoprodian (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 Isoprodian (Isoniazid) may exist. When ketoconazole is given in combination with Isoprodian (Isoniazid) and rifampin the AUC of ketoconazole is decreased by as much as 88% after 5 months of concurrent Isoprodian (Isoniazid) and rifampin therapy4.

Phenytoin

Isoprodian 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 Isoprodian (Isoniazid) and theophylline may cause elevated plasma levels of theophylline, and in some instances a slight decrease in the elimination of Isoprodian (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 Isoprodian. Plasma valproate concentration should be monitored when Isoprodian (Isoniazid) and valproate are co-administered, and appropriate dosage adjustments of valproate should be made8.

Carcinogenesis and Mutagenesis:

Isoprodian (Isoniazid) has been shown to induce pulmonary tumors in a number of strains of mice. Isoprodian (Isoniazid) has not been shown to be carcinogenic in humans. (Note: a diagnosis of mesothelioma in a child with prenatal exposure to Isoprodian (Isoniazid) and no other apparent risk factors has been reported). Isoprodian (Isoniazid) has been found to be weakly mutagenic in strains TA 100 and TA 1535 of Salmonella typhimurium (Ames assay) without metabolic activation.

Pregnancy

Teratogenic effects: Pregnancy Category C

Isoprodian has been shown to have an embryocidal effect in rats and rabbits when given orally during pregnancy. Isoprodian (Isoniazid) was not teratogenic in reproduction studies in mice, rats and rabbits. There are no adequate and well-controlled studies in pregnant women. Isoprodian (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 Isoprodian (Isoniazid) in breast milk do not threaten the neonate. Since Isoprodian (Isoniazid) is known to cross the placental barrier, neonates of Isoprodian (Isoniazid) treated mothers should be carefully observed for any evidence of adverse affects.

Nonteratogenic effects

Since Isoprodian (Isoniazid) is known to cross the placental barrier, neonates of isoniazid-treated mothers should be carefully observed for any evidence of adverse effects.

Nursing Mothers

The small concentrations of Isoprodian (Isoniazid) in breast milk do not produce toxicity in the nursing newborn; therefore, breast feeding should not be discouraged. However, because levels of Isoprodian (Isoniazid) are so low in breast milk, they can not be relied upon for prophylaxis or therapy of nursing infants.

ADVERSE REACTIONS

The most frequent reactions are those affecting the nervous system and the liver.

Nervous System Reactions - Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics), and is usually preceded by paresthesias of the feet and hands. The incidence is higher in "slow inactivators".

Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment, and toxic psychosis.

Hepatic Reactions - See boxed WARNING. Elevated serum transaminase (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice, and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise, and weakness. Mild hepatic dysfunction, evidenced by mild and transient elevation of serum transaminase levels occurs in 10% to 20% of patients taking Isoprodian (Isoniazid). This abnormality usually appears in the first 1 to 3 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal, and generally, there is no necessity to discontinue medication during the period of mild serum transaminase elevation. In occasional instances, progressive liver damage occurs, with accompanying symptoms. If the SGOT value exceeds three to five times the upper limit of normal, discontinuation of the Isoprodian (Isoniazid) should be strongly considered. The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age.

Gastrointestinal Reactions - Nausea, vomiting, and epigastric distress.

Hematologic Reactions - Agranulocytosis; hemolytic, sideroblastic, or aplastic anemia, thrombocytopenia; and eosinophilia.

Hypersensitivity Reactions - Fever, skin eruptions (morbilliform, maculopapular, purpuric, or exfoliative), lymphadenopathy, and vasculitis.

Metabolic and Endocrine Reactions - Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis, and gynecomastia.

Miscellaneous Reactions - Rheumatic syndrome and systemic lupus erythematosus-like syndrome.

To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, and the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

Signs and Symptoms

Isoprodian overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision, and visual hallucinations (including bright colors and strange designs) are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe, intractable seizures. Severe metabolic acidosis, acetonuria, and hyperglycemia are typical laboratory findings.

Treatment

Untreated or inadequately treated cases of gross Isoprodian (Isoniazid) overdosage, 80 mg/kg - 150 mg/kg, can cause neurotoxicity6 and terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion.

For the Asymptomatic Patient

Absorption of drugs from the GI tract may be decreased by giving activated charcoal. Gastric emptying should also be employed in the asymptomatic patient. Safeguard the patient"s airway when employing these procedures. Patients who acutely ingest > 80 mg/kg should be treated with intravenous pyridoxine on a gram per gram basis equal to the Isoprodian dose. If an unknown amount of Isoprodian (Isoniazid) is ingested, consider an initial dose of 5 grams of pyridoxine given over 30 to 60 minutes in adults, or 80 mg/kg of pyridoxine in children.

For the Symptomatic Patient

Ensure adequate ventilation, support cardiac output, and protect the airway while treating seizures and attempting to limit absorption. If the dose of Isoprodian (Isoniazid) is known, the patient should be treated initially with a slow intravenous bolus of pyridoxine, over 3 to 5 minutes, on a gram per gram basis, equal to the Isoprodian (Isoniazid) dose. If the quantity of Isoprodian (Isoniazid) ingestion is unknown, then consider an initial intravenous bolus of pyridoxine of 5 grams in the adult or 80 mg/kg in the child. If seizures continue, the dosage of pyridoxine may be repeated. It would be rare that more than 10 grams of pyridoxine would need to be given. The maximum safe dose for pyridoxine in Isoprodian (Isoniazid) intoxication is not known. If the patient does not respond to pyridoxine, diazepam may be administered. Phenytoin should be used cautiously, because Isoprodian (Isoniazid) interferes with the metabolism of phenytoin.

General

Obtain blood samples for immediate determination of gases, electrolytes, BUN, glucose, etc.; type and cross-match blood in preparation for possible hemodialysis.

Rapid control of metabolic acidosis

Patients with this degree of INH intoxication are likely to have hypoventilation. The administration of sodium bicarbonate under these circumstances can cause exacerbation of hypercarbia. Ventilation must be monitored carefully, by measuring blood carbon dioxide levels, and supported mechanically, if there is respiratory insufficiency.

Dialysis

Both peritoneal and hemodialysis have been used in the management of Isoprodian (Isoniazid) overdosage. These procedures are probably not required if control of seizures and acidosis is achieved with pyridoxine, diazepam and bicarbonate.

Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, utilize meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration, pneumonitis, etc.

DOSAGE AND ADMINISTRATION

: NOTE: For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: (1) the recommendations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42; RR-4, 1993 and (2) Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149; 1359-1374, 1994.

For Treatment of Tuberculosis - Isoprodian (Isoniazid) is used in conjunction with other effective anti-tuberculosis agents. Drug susceptibility testing should be performed on the organisms initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli become resistant, therapy must be changed to agents to which the bacilli are susceptible.

Usual Oral Dosage (depending on the regimen used):

  • Adults: 5 mg/kg up to 300 mg daily in a single dose; or

    15 mg/kg up to 900 mg day, two or three times/week

  • Children: 10-15 mg/kg up to 300 mg daily in a single dose; or

    20-40 mg/kg up to 900 mg/day, two or three time/week

Patients with Pulmonary Tuberculosis Without HIV Infection

There are 3 regimen options for the initial treatment of tuberculosis in children and adults:

Option 1: Daily Isoprodian (Isoniazid), rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of Isoprodian (Isoniazid) and rifampin daily or 2-3 times weekly. Ethambutol or streptomycin should be added to the initial regimen until sensitivity to Isoprodian (Isoniazid) and rifampin is demonstrated. The addition of a fourth drug is optional if the relative prevalence of isoniazid-resistant Mycobacterium tuberculosis isolates in the community is less than or equal to four percent.

Option 2: Daily Isoprodian (Isoniazid), rifampin, pyrazinamide, and streptomycin or ethambutol for 2 weeks followed by twice weekly administration of the same drugs for 6 weeks, subsequently twice weekly Isoprodian (Isoniazid) and rifampin for 16 weeks.

Option 3: Three times weekly with Isoprodian (Isoniazid), rifampin, pyrazinamide, and ethambutol or streptomycin for 6 months.

*All regimens given twice weekly or 3 times weekly should be administered by directly observed therapy.

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 Isoprodian (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.

Patients with Pulmonary Tuberculosis and HIV Infection

The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness. For this reason, therapeutic decisions for the impaired host must be individualized. Since patients co-infected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of MDRTB.

Patients with Extra pulmonary Tuberculosis

The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease. Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective. Because of the insufficient data, miliary tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 months therapy.

Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative inaccessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings.

The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Pott's Disease. Corticosteriods have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.

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 Isoprodian and rifampin. Ethambutol should be included unless primary Isoprodian (Isoniazid) resistance is unlikely (isoniazid resistance rate documented to be less than 4%).

Treatment of Patients with Multi-Drug Resistant Tuberculosis (MDRTB)

Multiple-drug resistant tuberculosis (i.e., resistance to at least Isoprodian (Isoniazid) and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended.

Directly Observed Therapy

A major cause of drug-resistant tuberculosis is patient non-compliance with treatment. The use of DOT can help assure patient compliance with drug therapy. DOT is the observation of the patient by a health care provider or other responsible person as the patient ingests anti-tuberculosis medications. DOT can be achieved with daily, twice weekly or thrice weekly regimens, and is recommended for all patients.

For Preventative Therapy of Tuberculosis

Before Isoprodian (Isoniazid) preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Appropriate evaluations should be performed if Extra pulmonary tuberculosis is suspected.

Adults over 30 Kg: 300 mg per day in a single dose.

Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose. In situations where adherence with daily preventative therapy cannot be assured, 20-30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of administration8.

Continuous administration of Isoprodian (Isoniazid) for a sufficient period is an essential part of the regimen because relapse rates are higher if chemotherapy is stopped prematurely. In the treatment of tuberculosis, resistant organisms may multiply and the emergence of resistant organisms during the treatment may necessitate a change in the regimen.

For following patient compliance: the Potts-Cozart test9, a simple colorimetric6 method of checking for Isoprodian (Isoniazid) in the urine, is a useful tool for assuring patient compliance, which is essential for effective tuberculosis control. Additionally, Isoprodian (Isoniazid) test strips are also available to check patient compliance.

Concomitant administration of pyridoxine (B6) is recommended in the malnourished and in those predisposed to neuropathy (e.g., alcoholics and diabetics).

HOW SUPPLIED

Isoprodian (Isoniazid) Tablets, USP 100 mg: White, Round Tablets; Debossed "West-ward" on one side and "260" on the Scored side.

  • Bottles of 100 tablets
  • Bottles of 1000 tablets
  • Unit Dose Boxes of 100 tablets

Isoprodian (Isoniazid) Tablets, USP 300 mg: White, Round Tablets; Debossed "West-ward 261" on one side and Scored on the other side.

  • Bottles of 30 tablets
  • Bottles of 100 tablets
  • Bottles of 1000 tablets
  • Unit Dose Boxes of 100 tablets

Store at 20-25°C (68-77°F). Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

References

  • Murphy, R., et al: Annuals of Internal Medicine; 1990: November 15; volume 113:799-800.
  • Burke, R.F., et al: Res Commun Chem Pathol Pharmacol. 1990;J uly; vol. 69; 115-118.
  • Fleenor, M.F., et al: Chest (United States) Letter; 1991: June; 99(6): 1554.
  • Baciewicz, A.M. and Baciewicz,Jr. F.A.,: Arch Int Med 1993, September; volume 153;1970-1971.
  • Jonville, A.P., et al: European Journal of Clinical Pharmacol (Germany), 1991: 40(2) p198.
  • American Thoracic Society/Centers for Disease Control: Treatment of Tuberculosis and Tuberculosis Infection in

    Adults and Children. Amer. J. Respir Crit Care Med.1994; 149: p 1359-1374.

  • Hoglund P.,et al: European Journal of Respir Dis (Denmark) 1987: February; 70(2) p110-116.
  • Committee on Infectious Diseases American Academy of Pediatrics: 1994, Red Book: Report of the

    Committee on Infectious Diseases; 23rd edition; p487.

  • Schraufnagel, DE; Testing for Isoprodian (Isoniazid); Chest (United States) 1990, August: 98(2) p314-316.

Manufactured by:

West-ward Pharmaceutical Corp.

Eatontown, NJ 07724

Revised February 2011

Isoprodian (Isoniazid) 300mg Tablet

Structural Formula

Isoprodian pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Isoprodian available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Isoprodian destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Isoprodian Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Isoprodian pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."ISONIAZID TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."DAPSONE TABLET [JACOBUS PHARMACEUTICAL COMPANY, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."ISONIAZID; RIFAMPIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Isoprodian?

Depending on the reaction of the Isoprodian after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Isoprodian not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Isoprodian addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Isoprodian, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Isoprodian consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

One visitor reported side effects

Did you get side effects while taking the Isoprodian drug, or were there no side effects?
According to the survey conducted by website sdrugs.com users, the below-mentioned percentages indicate the number of people experiencing the side effects and the number of people not experiencing the side effects when taking Isoprodian medicine. Every drug produces minimal side effects, and they are negligible most times, when compared to the desired effect [use] of the medicine. Side effects depend on the dose you are taking, any drug interactions that happen when you are on other medications, if the patient is sensitive, and other associated conditions. If you cannot tolerate the side effects, consult your doctor immediately, so he can either adjust the dose or change the medication.
Visitors%
No side effects1
100.0%

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

One visitor reported age

Visitors%
> 601
100.0%

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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