Forecox

Each film-coated tablet contains Rifampicin (Forecox) 150 mg, Isoniazid (Forecox) 75 mg, Pyrazinamide (Forecox) 400 mg and Ethambutol (Forecox) HCl 275 mg.

Forecox is a 4-drug fixed-dose combination (FDC) of antituberculosis drugs Rifampicin (Forecox), Isoniazid (Forecox), Pyrazinamide (Forecox) and Ethambutol (Forecox) HCl developed as per the recommendations of World Health Organization (WHO), which offers the ease of administration and facilitates patient compliance in the treatment of tuberculosis.

Initial phase treatment and re-treatment of all forms of tuberculosis in category I and category II patients caused by susceptible strains of mycobacteria.

Category I: New cases of smear-positive pulmonary tuberculosis and other newly diagnosed seriously ill patients with severe forms of tuberculosis.

Category II: Relapse or treatment failure patients.

The recommended dosage and treatment regimen for tuberculosis is dependent on the patient's medical history, response to treatment and the sensitivity of the isolate. Dosage should be consistent with guidelines issued by the World Health Organization (WHO).

Adults: For Category I patients, Forecox is given daily during the initial phase (8 weeks) of treatment. If sputum is smear-positive after the initial 8 weeks, the initial phase treatment with Forecox should be continued for a further 4 weeks.

For Category II patients, Forecox is given daily during the initial phase (12 weeks) of treatment. Streptomycin should be given in addition to Forecox during the first 8 weeks of the initial phase. If sputum is smear-positive after the initial 12 weeks of treatment, Forecox should be given for an additional 4 weeks. Patients in category II are at an increased risk of developing multidrug resistant disease and should receive fully supervised treatment for at least the first 12 weeks.

WHO guidelines indicate that Forecox should be given daily during the initial phase treatment of Category I and II patients with the dose adjusted according to body weight, as follows: Patients Weighing >71 kg: 5 tablets; 55-70 kg: 4 tablets; 40-54 kg: 3 tablets.

Forecox should not be used to treat patients of low body weight (<40 kg).

Category I and II patients, who are still sputum smear-positive after completion of the initial phase, should be evaluated for further treatment according to WHO or local guidelines for the treatment of tuberculosis.

Children: The efficacy of the combination has not been established in children, and Forecox should not be used in children <13 years of age since safe conditions for use have not been established.

Elderly: As with any drug, caution should be exercised when using Forecox to treat elderly patients.

Renal Insufficiency: Ethambutol (Forecox) accumulates in patients with renal insufficiency. Pyrazinamide (Forecox) is also excreted thru the kidney as unchanged drug. If renal impairment is severe or if patients are slow acetylators, a reduction in dosage may be required.

Hepatic Insufficiency: Dose adjustment of Forecox may be necessary in patients with hepatic insufficiency or patients who are slow acetylators. Patients with acute or chronic liver disease and patients who are slow acetylators have higher serum Isoniazid (Forecox) concentrations and exhibit a longer serum t_½ for Isoniazid (Forecox). The plasma t_½ of Pyrazinamide (Forecox) may be prolonged in patients with hepatic insufficiency. The clearance of Rifampicin (Forecox) is significantly decreased in patients with liver disease.

Administration: Forecox should be taken 1 hr before or 2 hrs after a meal. Should gastrointestinal irritation occur, the combination may be taken with food or antacids, but not aluminum-containing antacids.

Known hypersensitivity to Ethambutol (Forecox), Isoniazid (Forecox), Rifampicin (Forecox) or Pyrazinamide (Forecox), or to any of the excipients of Forecox.

In the presence of alcoholism, optic neuritis, impaired hepatic function and severe renal insufficiency, hyperuricemia and/or gouty arthritis, in the presence of jaundice or in patients with known retrobulbar neuritis unless the doctor determines that it may be used.

Patients who are unable to appreciate and report visual side effects or changes in vision (eg, young children and patients with mental illness or mental deficiency).

Pyrazinamide (Forecox): Patients with severe hepatic damage; on concomitant therapy with Rifampicin (Forecox) who are concurrently taking other medications associated with liver injury, drink excessive amounts of alcohol (even if alcohol use is discontinued during treatment), have underlying liver disease, or have a history of Isoniazid (Forecox)-associated liver injury.

Rifampicin (Forecox): Para-aminosalicylic acid, clofazimine and dapsone decrease the effects of Rifampicin (Forecox).

Rifampicin (Forecox) decreases the effects of paracetamol, oral anticoagulants, barbiturates, benzodiazepines, β-blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, mexiletine, quinidine, sulfones, sulfonylureas, theophylline, tocainide and verapamil.

Halothane and Isoniazid (Forecox) when co-administered with Rifampicin (Forecox) may result in a higher rate of hepatotoxicity than with either agent alone. If alterations in liver function tests occur, consider discontinuation of 1 or both drugs.

Concomitant administration with ketoconazole may produce low serum concentrations of each drug, resulting in failure of antifungal therapy.

Drug/Food Interaction: Food interferes with the absorption of Rifampicin (Forecox), possibly resulting in decreased peak plasma concentrations. Take on an empty stomach.

Isoniazid (Forecox): Isoniazid (Forecox) inhibits the metabolism of anticonvulsants, benzodiazepines, haloperidol, ketoconazole, theophylline and warfarin.

Concomitant antacid administration may reduce the absorption of Isoniazid (Forecox).

Corticosteroids may decrease the serum concentrations of Isoniazid (Forecox) by increasing acetylation rate and/or renal clearance. Para-aminosalicylic acid may increase the plasma concentration and elimination half-life of Isoniazid (Forecox) by competition of acetylating enzymes.

Isoniazid (Forecox) may produce hypoglycemia and lead to loss of glucose control in patients on oral hypoglycemics.

Fast acetylation of Isoniazid (Forecox) may produce high concentrations of hydrazine, which facilitate defluorination of enflurane.

Pyrazinamide (Forecox): Pyrazinamide (Forecox) interferes with oral antidiabetics or with medicines taken for the treatment of gout.

Laboratory Test Interactions: Pyrazinamide (Forecox) interferes with Acetest and Ketostix urine tests to produce pink-brown color.

Ethambutol (Forecox): Aluminum salts found in antacids may delay and reduce the absorption of Ethambutol (Forecox). Separate their administration by several hours.

Each component of Forecox has specific reported adverse reactions described as follows.

Ethambutol (Forecox): The following reactions have occurred with Ethambutol (Forecox). Since Ethambutol (Forecox) is a component of Forecox, these reactions may also occur with use of Forecox.

Blood and Lymphatic System Disorders: Leukopenia, thrombocytopenia, neutropenia.

Immune System Disorders: Anaphylactic/anaphylactoid reaction (including shock and fatalities). Hypersensitivities syndrome consisting of cutaneous reaction (eg, rash or exfoliative dermatitis), eosinophilia and ≥1 of the following: Hepatitis, pneumonitis, nephritis, myocarditis and pericarditis. Fever and lymphadenopathy may be present.

Metabolism and Nutrition Disorders: Anorexia, elevations of serum uric acid concentration.

Nervous System Disorders: Dizziness, hypoesthesia, paresthesia.

Eye Disorders: Ethambutol (Forecox) may produce decreases in visual acuity including irreversible blindness, which appear to be due to optic neuritis. This effect may be related to dose and duration of treatment, and patients receiving Ethambutol (Forecox) for prolonged periods at doses >20 mg/kg have an increased risk of developing optic neuritis. This effect is generally reversible when administration of the drug is discontinued promptly and recovery of visual acuity generally occurs over a period of weeks to months after the drug has been discontinued. Some patients have received Ethambutol (Forecox) again after such recovery without recurrence of visual acuity loss. However, in rare cases recovery may be delayed for up to ≥1 year and irreversible blindness has also been reported. In addition, children and adults of low body weight (<40 kg) have an increased risk of developing optic neuritis. Because Ethambutol (Forecox) has a unique effect on the eye, it is recommended that patients undergo a full ophthalmologic examination before starting treatment and periodically during drug administration.

This examination should include visual acuity, color vision, perimetry and ophthalmoscopy. Because Forecox may have adverse effects on vision, physical examination should include ophthalmoscopy, finger perimetry and testing of color discrimination. In patients with visual defects eg, cataracts, recurrent inflammatory conditions of the eye, optic neuritis and diabetic retinopathy, the evaluation of changes in visual acuity is more difficult and care should be taken to be sure that variations in vision are not due to the underlying disease conditions. In such patients, consideration should be given to relationship between benefits expected and possible visual deterioration since evaluation of visual changes is difficult. The change in visual acuity may be unilateral or bilateral and hence, each eye must be tested separately and both eyes tested together. Testing of visual acuity should be performed before beginning Ethambutol (Forecox) therapy and periodically during medicine administration, except that it should be done once monthly when the patient is on a dosage of ≥15 mg/kg/day. Snellen eye charts are recommended for testing of visual acuity. Clinical studies have shown that there are definite fluctuations of 1 or 2 lines of the Snellen chart in the visual acuity of many tuberculous patients not receiving Ethambutol (Forecox).

The following table may be useful in interpreting possible changes in visual acuity attributable to Ethambutol (Forecox).

In general, changes in visual acuity less than those indicated under 'Significant Number of Lines' and 'Decrease Number of Points', may be due to chance findings, limitations of the testing method or physiologic variability. Conversely, changes in visual acuity equalling or exceeding those under 'Significant Number of Lines' and 'Decrease Number of Points' indicate need for retesting and careful evaluation of the patient's visual status. If careful evaluation confirms that magnitude of visual change and fails to reveal another cause, Ethambutol (Forecox) should be discontinued and the patient re-evaluated at frequent intervals. Progressive decreases in visual acuity during therapy must be considered to be due to Ethambutol (Forecox).

If corrective glasses are used prior to treatment, these must be worn during visual acuity testing. During 1-2 years of therapy, a refractive error may develop which must be corrected in order to obtain accurate test results. Testing of visual acuity through a pinhole eliminates the refractive error. Patients developing visual abnormality during Ethambutol (Forecox) treatment may show subjective visual symptoms before, or simultaneous with the demonstration of decreases in visual acuity, and all patients receiving Ethambutol (Forecox) should be questioned periodically about blurred vision and other subjective eye symptoms.

In addition, visual field defect, color blindness, scotoma, optic neuropathy and retrobulbar neuritis have been reported.

Patients should be advised to report promptly to their physician any change in visual acuity.

Gastrointestinal Disorders: Epigastric distress, constipation, nausea, vomiting, abdominal pain, anorexia, metallic taste, dry mouth.

Hepatobiliary Disorders: Impairment of liver function, as indicated by abnormalities in liver function tests and liver toxicities including fatalities, has been reported. Jaundice and transient liver dysfunction have also been reported. Because Ethambutol (Forecox) is recommended for therapy in conjunction with ≥1 other antituberculosis drugs, these changes may be related to concurrent therapy.

Skin and Subcutaneous Tissue Disorders: Pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal, Connective Tissue and Bone Disorders: Joint pains, acute gout.

Respiratory, Thoracic and Mediastinal Disorders: Pulmonary infiltrates with or without eosinophilia.

Renal and Urinary Disorders: Gout, hyperuricemia.

General Disorders and Administration Site Conditions: Malaise, fever.

Rifampicin (Forecox): The following reactions have occurred with Rifampicin (Forecox). Because Rifampicin (Forecox) is a component of Forecox, these reactions may also occur with use of Forecox.

Blood and Lymphatic System Disorders: Thrombocytopenia, leukopenia, hemolytic anemia, anemia, eosinophilia.

Thrombocytopenia has occurred when Ethambutol (Forecox) and Rifampicin (Forecox) were administered concomitantly according to an intermittent dose schedule twice weekly and in high doses.

Immune System Disorders: Hypersensitivity reactions.

Metabolism and Nutrition Disorders: Elevations in serum uric acid.

Nervous System Disorders: Headache, drowsiness, fatigue, ataxia, dizziness, inability to concentrate, mental confusion, muscular weakness, generalized numbness, pain in the extremities.

Eye Disorders: Visual disturbances, exudative conjunctivitis.

Gastrointestinal Disorders: Heartburn, nausea, vomiting, diarrhea, epigastric distress, anorexia, gas, cramps, sore mouth and tongue, fungal overgrowth.

Hepatobiliary Disorders: Hepatitis or hepatitis prodromal syndrome, shock-like syndrome with hepatic involvement, abnormal liver function tests (elevation in serum bilirubin, serum transaminases and alkaline phosphatase).

Hepatitis from Rifampicin (Forecox) may occur in patients with normal hepatic function. Chronic liver disease, alcoholism and old age appear to increase the incidence of severe hepatic problems when Rifampicin (Forecox) is given alone or concurrently with Isoniazid (Forecox).

Skin and Subcutaneous Tissue Disorders: Pruritus, urticaria, rash, pemphigoid reaction, purpura.

Renal and Urinary System Disorders: Elevations in blood urea nitrogen, interstitial nephritis, alteration in kidney function.

Hemolysis, hemoglobinuria, hematuria, renal insufficiency or acute renal failure have been reported and are generally considered to be hypersensitivity reactions. These have occurred during intermittent therapy or when treatment was resumed following intentional or accidental interruption of a daily dosage regimen and were reversible when Rifampicin (Forecox) was discontinued and appropriate therapy instituted.

Reproductive System and Breast Disorders: Menstrual disturbances.

General Disorders and Administration Site Conditions: Fever, flu-like syndrome.

Isoniazid (Forecox): The following reactions have occurred with Isoniazid (Forecox). Because Isoniazid (Forecox) is a component of Forecox, these reactions may also occur with use of Forecox.

Blood and Lymphatic System Disorders: Agranulocytosis, eosinophilia, anemia, thrombocytopenia, methemoglobinemia, vasculitis, lymphadenopathy.

Immune System Disorders: Allergic reactions, lupus-like syndrome, rheumatoid syndrome.

Hypersensitivity may result in fever, various skin eruptions, hepatitis, rash (including morbilliform, maculopapular, purpuric and urticarial), vasculitis and lymphedema.

Nervous System Disorders: Peripheral neuropathy is the most common toxic effect of Isoniazid (Forecox). It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (eg, alcoholics and diabetics), and is usually preceded by paresthesia of the feet and hands. The incidence is higher in slow acetylators. Isoniazid (Forecox) may cause peripheral neuritis by acting as a pyridoxine antagonist. Pyridoxine has been used successfully for prophylaxis and treatment of Isoniazid (Forecox)-induced peripheral neuritis.

Headache, insomnia, restlessness, mental confusion, toxic psychoses, increased reflexes, muscle twitching, paresthesias.

Convulsions have occurred in apparently normal individuals when given Isoniazid (Forecox) in high doses.

Eye Disorders: Optic neuritis and atrophy have been reported. Ophthalmologic examinations should be carried out wherever visual complaints occur.

Ear and Labyrinth Disorders: Tinnitus.

Metabolism and Nutrition Disorders: Pellagra, hyperglycemia, metabolic acidosis, gynecomastia.

Gastrointestinal Disorders: Epigastric distress, nausea, vomiting, constipation.

Hepatobiliary Disorders: Severe and sometimes fatal hepatitis may occur and may develop even after many months of treatment. The risk of developing hepatitis is age-related and is increased with daily consumption of alcohol.

Skin and Subcutaneous Tissue Disorders: Rash, exfoliative dermatitis.

Musculoskeletal, Connective Tissue and Bone Disorders: Arthritic symptoms.

Renal and Urinary Disorders: Urinary disturbance in male (prostatic obstruction syndrome), urinary retention.

General Disorders and Administration Site Conditions: Fever, dryness of the mouth.

Pyrazinamide (Forecox): The principal adverse effect is a hepatic reaction. Hepatotoxicity appears to be dose-related and may appear at any time during therapy. Jaundice, hepatitis and hepatic failure have been reported. Fatalities have been reported with hepatitis and hepatic failure. Increased hepatotoxicity may occur with the co-administration with other antituberculous medications.

The following reactions have occurred with Pyrazinamide (Forecox). Because Pyrazinamide (Forecox) is a component of Forecox, these reactions may also occur with use of Forecox: Blood and Lymphatic System Disorders: Thrombocytopenia, sideroblastic anemia with erythroid hyperplasia, vacuolation of erythrocytes, abnormalities in blood clotting mechanisms, porphyria.

Immune System Disorders: Hypersensitivity reactions including rash, urticaria, pruritus.

Metabolism and Nutrition Disorders: Anorexia, hyperuricemia. Increased difficulty has been reported in controlling diabetes mellitus when diabetics are given with Pyrazinamide (Forecox).

Gastrointestinal Disorders: Nausea, vomiting.

Hepatobiliary Disorders: The principal effect is a hepatic reaction. Hepatotoxicity appears to be dose-related and may appear at any time during therapy. Hepatitis and hepatic failure (including fatalities) have been reported. Patients may have increased liver enzymes, including AST and ALT and increased serum bilirubin. Hepatomegaly, splenomegaly and jaundice may develop.

Skin and Subcutaneous Tissue Disorders: Acne, photosensitivity, skin rashes.

Renal and Urinary System Disorders: Dysuria, interstitial nephritis.

Musculoskeletal, Connective Tissue and Bone Disorders: Arthralgia, gout, myalgia.

General Disorders: Fever, malaise.