Rimstar 4

Rifampicin, isoniazid, pyrazinamide, ethambutol HCl.

Each tablet contains rifampicin 150 mg, isoniazid 75 mg, pyrazinamide 400 mg and ethambutol HCl 275 mg. It also contains pregelatinized starch, maize starch, sodium lauryl sulfate, microcrystalline cellulose, povidone K30, crospovidone, magnesium stearate, purified talc, copovidone, hypromellose, titanium dioxide, polyethylene glycol 400, red iron oxide and polyethylene 6000 as other ingredients.

Rifampicin is a rifamycin antibiotic while isoniazid, pyrazinamide and ethambutol are specific antituberculous agents. Rifamycin and isoniazid are both bactericidal against Mycobacterium tuberculosis. Ethambutol is bacteriostatic against Mycobacterium tuberculosis. Rifampicin and ethambutol also exhibit variable activity against other atypical species of Mycobacterium.
The exact mechanism of action of pyrazinamide is unknown.

Management of tuberculosis and certain opportunistic mycobacterial infections. Rifampicin is effective in cases resistant to other antituberculous agents and shows no cross-resistance outside the rifamycin group of drugs.

The following information applies unless otherwise instructed by the doctor.
The total dosage requirement of rifampicin is 10 (8-12) mg/kg body mass/day, of isoniazid 5 (4-6) mg/kg body mass/day, of pyrazinamide 25 (20-30) mg/kg body mass/day and of ethambutol 15 (10-20) mg/kg body mass/day.
Each tablet contains rifampicin, isoniazid, pyrazinamide and ethambutol in such a ratio that the previously mentioned recommendations are achieved by giving 1 tab/15 kg body weight.
The daily dosage is calculated from the recommended daily requirement given previously: Patients with a body mass of ≥71 kg: 5 tablets daily; 55-70 kg: 4 tablets daily; 38-54 kg: 3 tablets daily; 30-37 kg: 2 tablets daily.
Hepatic and/or Renal Failure and in the Elderly: Rifampicin: In elderly patients, plasma concentrations are similar to those in young patients. Provided that hepatic excretory function is normal, the dosage in patients with impaired renal function need not be reduced below 600 mg daily. In the presence of severe hepatic dysfunction, the dosage may have to be adjusted accordingly. Rifampicin is eliminated by peritoneal or hemodialysis. Dosage adjustment is not necessary during dialysis.
Isoniazid: In elderly patients with impaired liver function or severely impaired renal function, it might be necessary to adapt the dosage accordingly to avoid unwanted effects.
Pyrazinamide: Dosage adjustment is not necessary.
Ethambutol: In the elderly, the dosage does not need adaptation. However in patients with impaired renal function, it might be necessary to reduce the dosage depending on the degree of renal impairment.
Administration: Nature and Duration: Rimstar 4 should be swallowed whole. The tablets should be given as a single dose, preferably on an empty stomach, at least 30 min before breakfast to ensure a high peak serum concentration.
Rimstar 4 is recommended in the initial intensive phase of the short-course treatment of pulmonary tuberculosis. During this phase which lasts for 2 months, Rimstar 4 should be administered on a continuous daily basis. This recommendation may vary corresponding to national treatment guidelines.

Symptoms: Rifampicin: Nausea, vomiting, abdominal pain, enlargement of the liver, jaundice, elevated liver enzymes, possible acute pulmonary edema, lethargy, clouding of consciousness, convulsions, generalized pruritus, brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears and feces.
Isoniazid: Early manifestations (within 30 min to 3 hrs): Nausea, vomiting, dizziness, slurring of speech, blurring of vision and visual hallucinations. With marked overdosage: Respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, severe, intractable seizures. Severe metabolic acidosis, acetonuria and hyperglycemia are typical laboratory findings.
Pyrazinamide: Abnormal liver function test, hyperuricemia.
Ethambutol HCl: Disturbances in sense organs and special senses, especially visual disturbances.
When overdosage occurs, immediately contact the physician to treat the patient accordingly.
Treatment: Gastric lavage is advised within the first 2-3 hrs after ingestion, but it should not be attempted until convulsions are under control.
Intensive supportive measures (eg, forced osmotic diuresis, hemodialysis, peritoneal dialysis, rapid control of acidosis, monitoring of fluid intake and output, obtaining of blood samples) should be instituted and individual symptoms treated as they arise (eg, treatment of convulsions).

Known or suspected hypersensitivity to rifamycins and/or to isoniazid, pyrazinamide and ethambutol and/or to any of the excipients of Rimstar 4. History of drug-induced hepatitis, acute liver diseases regardless of their origin, peripheral neuritis and optic neuritis.

Patients should abstain from alcohol while under treatment with Rimstar 4.
Rimstar 4 can permanently discolor soft contact lenses. Do not wear them while taking these tablets or for 1 week after stopping the medication.
To preclude the possibility of pregnancy during treatment with rifampicin, additional nonhormonal means of contraception must be employed (see Interactions).
In hyperuricemia accompanied by an acute gouty arthritis, the patient should be transferred to a regimen not containing pyrazinamide.

Caution is advised in patients with impaired renal, liver and visual function, diabetes mellitus, chronic alcoholism and undernourished patients, in patients with a history of gout and in patients suffering from convulsive disorders and acute porphyria.
The ethambutol component causes Rimstar 4 not to be recommended for children <8 years and in patients who are not able to communicate visual disturbances out of other reasons. The main reason is that the visual disturbances that may occur as a result of using Rimstar 4 and that require immediate discontinuation of the therapy are difficult to diagnose in little children.
Blood counts and liver function tests (SGPT and SGOT) should be performed periodically (especially in prolonged treatment) and at baseline, if possible.
Patients with current chronic liver disease or impaired liver function should be treated with caution and under strict medical supervision. Careful monitoring of liver function should be carried out and attention should be paid to possible prodromal symptoms of hepatitis eg, fatigue, weakness, malaise, anorexia, nausea or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, treatment should be discontinued promptly. The occurrence of severe and sometimes fatal hepatitis-associated infections may develop even after many months of treatment.
The occurrence of peripheral neuritis may be prevented by pyridoxine.
In patients with visual defects, Rimstar 4 should be used with care. Ethambutol HCl may affect acuity, color discrimination and visual field. It is advised to check the visual ability before starting treatment and to monitor this ability during treatment. If disturbances arise, treatment should be discontinued.
During Intermittent Therapy and Resumption of Therapy after its Interruption: Both temporary interruption of treatment and noncompliance (if the medication is not taken regularly) should, if possible, be avoided as potentially serious side effects can occur. If severe acute hypersensitivity reactions set in eg, thrombocytopenia, purpura, hemolytic anemia, dyspnea and asthma-like attacks, shock or renal failure, or other signs of hypersensitivity appear eg, fever or skin reactions, Rimstar 4 should be withdrawn.
Contact the physician where temporary withdrawal of Rimstar 4 is unavoidable.
Effects on the Ability to Drive or Operate Machinery: The ability to drive or operate machinery may be influenced by doses of ≥10 mg/kg of isoniazid by adversely affecting the reactions of the nervous system eg, peripheral neuropathy.
Use in pregnancy & lactation: Rimstar 4 should not be given during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Administration of rifampicin during the last few weeks of pregnancy can cause postnatal hemorrhage in the mother and newborn infant. This may necessitate treatment with vitamin K preparations. Although rifampicin, isoniazid, pyrazinamide and ethambutol pass into breast milk, no adverse effects on breastfed infants have been observed.
Since it is theoretically possible that isoniazid might exert neurotoxic effects on the child, prophylactic administration of pyridoxine to the mother during pregnancy and to the mother and child during breastfeeding is recommended.

Rimstar 4 should not be given during pregnancy unless the potential benefit justifies the potential risk to the fetus.
Administration of rifampicin during the last few weeks of pregnancy can cause postnatal hemorrhage in the mother and newborn infant. This may necessitate treatment with vitamin K preparations. Although rifampicin, isoniazid, pyrazinamide and ethambutol pass into breast milk, no adverse effects on breastfed infants have been observed.
Since it is theoretically possible that isoniazid might exert neurotoxic effects on the child, prophylactic administration of pyridoxine to the mother during pregnancy and to the mother and child during breastfeeding is recommended.

During Continuous Daily or Intermittent Therapy: Rifampicin-Associated: Rifampicin may cause reddish discoloration of body fluids and occasionally other body secretions eg, urine, sputum, lacrimal fluid, feces, saliva and sweat. It may permanently discolor soft contact lenses.
Hepatic Effects: Very common (>10%) is an asymptomatic increase in liver enzymes; severe life-threatening hepatic reactions eg, hepatic failure and acute fulminant hepatitis are uncommon (>0.1% and <1%). In isolated cases (<0.01%), a fatal outcome was observed.
Renal effects (eg, elevations of BUN and serum uric acid, hemolysis, hematuria, intestinal nephritis and renal insufficiency).
Gastrointestinal tract (eg, nausea, abdominal pains, vomiting or diarrhea, and pseudomembranous colitis).
Effects on the central and peripheral nervous system (eg, tiredness, drowsiness, headache, dizziness, ataxia, mental confusion, muscular weakness and visual disturbances).
Hematological changes (eg, leukopenia, eosinophilia, thrombocytopenia and thrombocytopenic purpura).
Effects on skin and appendages (eg, flushing, itching with or without skin rash, urticaria, reddening of the eyes, exudative conjunctivitis or generalised hypersensitivity reactions involving the skin eg, exfoliative dermatitis, Lyell's syndrome and pemphigoid reactions).
Endocrine effects (eg, disturbances in the menstrual cycle and induction of crisis in Addison patients).
During Intermittent Therapy or Upon Resumption of Treatment after Temporary Interruption: In patients taking rifampicin other than on a daily basis or in those resuming treatment with the drug after a temporary interruption, an influenza-like syndrome (flu syndrome) may occur, this being very probably of immunopathological origin. It is characterized by fever, shivering and possibly headache, dizziness and musculoskeletal pain. In rare cases the flu syndrome may be followed by thrombocytopenia, purpura, dyspnea, asthma-like attacks, hemolytic anemia, shock and acute renal failure. These serious complications may, however, also set in suddenly with no preceding flu syndrome, chiefly when treatment is resumed after a temporary interruption or when rifampicin is given only once a week in high doses (≥25 mg/kg). When rifampicin is administered in lower doses (600 mg) 2-3 times a week, the syndrome is encountered less frequently, its incidence then being comparable to that observed during daily medication.
Isoniazid-Associated: Hepatic effects (eg, disturbances of liver function and hepatitis). The common prodromal symptoms of severe hepatitis are anorexia, nausea, vomiting, fatigue, malaise and weakness. The frequency of progressive liver damage increases with age. It is rare in persons <20, but occurs in up to 2.3% of those >50 years.
Gastrointestinal effects (eg, nausea, vomiting and epigastric distress).
Effects on the central nervous system (eg, peripheral neuropathy usually preceded by paraesthesias of feet and hands, damage to the optic nerve, convulsions, psychoses, dizziness, lightheadedness, headache and toxic encephalopathy).
Hematological changes (eg, agranulocytosis, eosinophilia, thrombocytopenia and anemia).
Allergic and miscellaneous reactions (eg, drug rash, fever, dryness of the mouth, heartburn, disorders of micturition, rheumatic syndrome, lupus erythematosus-like signs and symptoms, pellagra, gynecomastia, vasculitis, lymphadenopathy, hyperglycemia and metabolic acidosis).
Pyrazinamide-Associated: Hepatic effects (eg, transient rises in serum transaminase level, hepatotoxicity, hepatomegaly and jaundice).
Renal effects (eg, hyperuricemia, intestinal nephritis and dysuria).
Gastrointestinal reactions (eg, nausea, vomiting and anorexia).
Hematological changes (thrombocytopenia, sideroblastic anemia and adverse effects on blood clotting mechanisms).
Allergic and miscellaneous effects (mild arthralgia and myalgia, skin rash, photosensitivity, urticaria, pruritus, fever, acne and porphyria).
Ethambutol-Associated: Effects on the central and peripheral nervous system (eg, confusion, disorientation, hallucinations, headache, dizziness and malaise).
Visual disturbances (eg, neuritis causing a restriction in visual acuity, constriction of visual field, dark spots in the visual field and red-green color blindness).
Hepatic effects (eg, jaundice and transient liver dysfunction).
Gastrointestinal effects (eg, nausea, vomiting, anorexia and abdominal pain).
Hematological changes (eg, leucopenia and thrombocytopenia).
Allergic effects and miscellaneous effects (eg, skin rash, pruritus, fever and joint pains) (rarely).
Acute gout (rarely).

Notify the physician when the following drugs are being taken or have been taken recently: Oral contraceptives or hormone replacement therapies; anticoagulants; tablets for diabetes, high blood pressure, heart disorders or epilepsy; medicines for stomach problems including antacids and cimetidine; medications for pain eg, morphine or codeine; disulfiram (a medicine used to treat drinking problems); medicines for anxiety or sleeplessness; medicines for gout, medications containing sulfinpyrazone, allopurinol, colchicine, probenecid; steroid tablets; chloramphenicol or ketoconazole; dapsone, methadone or theophylline; cyclosporin A or azathioprine; diuretics; and medicines with potential of neurotoxicity.
Rifampicin can delay the biliary excretion of contrast media employed in the x-ray of the gallbladder. Microbiological techniques for assaying folic acid and vitamin B12 in the serum are unsuitable for use during treatment with rifampicin.
Rifampicin causes temporary competitive inhibition of bromsulphthalein excretion. Tyramine- (cheese, red wine) and histamine- (tuna, tropical fish) containing foods should be avoided in patients receiving Rimstar 4.

Store at temperatures not exceeding 30°C. Protect from heat, light and moisture.

Anti-TB Agents

J04AM06 - rifampicin, pyrazinamide, ethambutol and isoniazid ; Belongs to the class of combination drugs used in the systemic treatment of tuberculosis.

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