COMPOSITIONS :
Rifampicin Film coated caplet 600 mg, each film coated caplet contains : Rifampicin 600 mg.
DESCRIPTIONS :
Rifampicin contains Rifampicin as active ingredient is available as film coated caplet 450 mg and 600 mg.
INDICATIONS :
- Rifampicin is indicated for tuberculosis therapy caused by Mycobacterium tuberculosis in combination with another antituberculosis agents.
- Rifampicin also used in combination with at least one antileprosy agents in multibaciller and paucibaciller leprosy therapy, by changing the infectious condition into non-infectious condition.
DOSAGE AND ADMINISTRATIONS :
Dosage :
- Tuberculosis :
Adults in single dose :
Dose for patients whose body weight < 50 kg is 450 mg daily. Patients whose body weight
> 50 kg is 600 mg daily. For patients with hepatic impairment, the dose should not more than 8 mg/kgBW.
Children :
10 – 20 mg/kgBW recommended daily dose. However, the total daily dose should not more than 600 mg.
Elderly :
Renal excretion of Rifampicin decreases with decreased kidney function, causing an increase in compensatory liver, half-life in serum of patient with young age. However, elevated levels in the blood have been reported in elderly patients on Rifampicin research, attention should be given in the use of Rifampicin against patients, particularly if proven impairment of renal function.
- Leprosy
For the treatment of leprosy, the WHO recommends the following regimen :
Leprosy multibaciller :
Rifampicin 600 mg, once monthly under supervision + Dapsone 100 mg, once daily as swamedication + Clofazimine (Lamprene) 300 mg, once monthly under supervision + 50 mg, once daily as swamedication. Duration of the treatment at least for 2 years.
Leprosy pausibaciller :
Rifampicin 600 mg, once monthly under supervision + Dapsone 100 mg ( 1 – 2 mg/kgBW) once daily. Duration of the treatment is 6 months.
Administration :
To ensure an optimal absorption, Rifampicin should be given on an empty stomach (1 hour before or 2 hours after meal). If given together with food, it can increase the gastrointestinal tolerance, which may affect to the bioavailability.
OVERDOSAGE :
Symptoms :
Nausea, vomiting, abdominal pain, pruritus, headache and increasing lethargy will occur in a short time after consumed the drug, unconsciousness can occur in patients with severe liver disease. The temporary enhancement of liver enzymes and/or bilirubin can occur. Reddish orange discoloration of the skin, urine, sweat, saliva, tears, and feces will occur, and the intensity accordance to the amount taken. Facial edema or periorbital also reported on pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and heart blockage have been reported in some fatal cases.
Treatment of overdosage :
Rinse the gastric within a few hours after taking the drug. A very large dose of Rifampicin can depresses the function of the nervous center. There is no specific antidote and supporting treatment.
CONTRAINDICATIONS :
- Patients who are hypersensitive to the active substance or an additional drug substance.
- Patients with acute liver disease, jaundice or severe liver disorders.
WARNINGS AND PRECAUTIONS :
- In the long-term use, in case of serious immunological reactions that result in impaired renal function, hemolytic or thrombocytopenia, the use of Rifampicin should be immediately stopped permanently.
- On long term treatment, clinical monitoring (and liver function tests, if possible) should be done to the patient with liver disease, which showed an increased risk of further liver damage.
- Patients should be warned that treatment with Rifampicin can cause redness on the secretion of body (urine, tears, saliva, sweat, semen and sputum) and contact lenses as well as clothes can be tarnished permanently.
- Rifampicin should be used with caution in patients with a history of diabetes mellitus, because handling in patients of diabetes mellitus is more difficult. The use of Rifampicin can reduce the effectiveness of oral anti diabetic drugs (Sulphonylurea) so that, anti diabetic drug dosages need to be improved.
- Administration of Rifampicin with the absence of strong evidence or diagnose of a bacterial infection or a prophylactic indication will not provide benefits to the patient and it only increase the risk of the development drug resistance to the bacteria.
- For the treatment of tuberculosis, Rifampicin is used in the daily dose. A dose of Rifampicin is greater than 600 mg given 1 or 3 times a week caused the occurrence side effects, including “flu syndrome” (fever, chills and malaise), hematopoietic reactions (leucopenia, thrombocytopenia, or acute hemolytic anemia), coetaneous reactions, gastrointestinal and hepatic, shortness of breath, shock, anaphylaxis and impaired renal function. Recent research indicates the use of 3 times a week dose of Rifampicin 600 mg + Isoniazide 15 mg/kgBW may be more tolerable.
- Rifampicin is not recommended for intermittent therapy, patient must be informed about termination treatment with intentionally or accidentally against daily doses regimen because renal hypersensitive reactions who rarely reported.
- Rifampicin is an induction enzyme that can increase endogenous substratum metabolism including adrenaline hormone, thyroid hormone and vitamin D. Rifampicin and Isoniazide can change vitamin D metabolism. In some cases may lower the levels vitamin D 25-hidroxy and vitamin D 1,25-hidroxy followed by decreased calcium and phosphate serum, and improve the parathyroid hormone.
- Laboratorium test :
The treatment of tuberculosis with Rifampicin in adults should be based on the measurement of hepatic enzymes, bilirubin, creatinine serum, complete blood count, platelet count. The test is not necessary for the children, except the complex conditions known or suspected clinically. The patient should be checked at least every month during therapy and there should be a specific question about the symptoms associated with the side effects. All patients with an abnormality must be acted upon, including laboratory tests, if necessary. Routine laboratory monitoring for toxicity in patients with normal measurement is generally not required.
- Use during pregnancy :
Rifampicin used on pregnant woman only if the benefits outweigh the risk. Use Rifampicin on the third trimester, mother and babies need to accompany by administering Vitamin K to prevent bleeding after childbirth.
- Use in lactation :
Rifampicin excreted through breast milk. However, the concentration in breast milk is very low, so that breastfeeding is not reliable for tuberculosis prophylaxis or therapy for infant breastfeeding. Not reported any adverse effects on the baby.
- Effects on ability to operate vehicles and engines :
There are no studies on the effect of Rifampicin on ability to drive and run the engine.
DRUG INTERACTIONS :
- Antacids, opioids, anti cholinergic and Ketoconazole decrease Rifampicin bioavailability when given orally together. To avoid this interaction, Rifampicin should be given a few hours before using the drug.
- Rifampicin highly potent to induce liver and digestive enzyme cytochrome P-450 and glucoronidation and P-glycoprotein transport system. Giving Rifampicin with drug that had biotransformation through these metabolic pathways, tend to accelerate the elimination of the drug when used together. This effect are close to the maximum after about 10 days of treatment, and gradually return to normal within 2 weeks or more after stopping the drug. This should be taken into account when treatment is done in conjunction with other medications. To maintain optimal blood levels, doses of drugs that are metabolized by these enzymes require dosage adjustment when starting or stopping medication along with Rifampicin following :
- Anti-infection (including certain antiretroviral drug, Mefloquine, Azole antifungal drugs, Clarithromycin, Erythromycin, Doxycycline, Atovaquon and Chloramphenicol).
- Hormone therapy, including Ethynilestradiol, Norethindrone, Tamoxifen and Levothyroxine.
- Methadone.
- Warfarin.
- Cyclosporine.
- Corticosteroid.
- Anti-seizure (include Phenytoin).
- Cardiovaskular agent, include Digoxin (in patient with renal insuficiency), Digitoxin, Verapamil, Nifedipine, Diltiazem, Propranolol, Metoprolol, Enalapril, Losartan, Quinidine, Mexiletine, Tocainide dan Propafenone.
- Theophylline.
- Hypoglichemic drug Sulphonylurea.
- Hypolipidemia, include Simvastatin dan Fluvastatin.
- Nortriptyline, Haloperidol, Quetiapine, Benzodiazepine, (include Diazepam, Triazolam), Zolpidem dan Buspirone.
- Clofibrate, Dapsone, Disopyramide, PAS preparation contains Bentonite (Aluminium hydrosilicate).
- Rifampicin interacts with hormonal contraceptives (KB pills, KB injections and KB implant) that may decrease the effectiveness of contraceptives. A tuberculosis patient should use non-hormonal contraceptives or contraceptive containing Estrogen high dose (50 µg).
- Antiretroviral drugs currently available (Non-Nucleoside Reverse Transcriptase Inhibitors and Protease Inhibitors) interact with Rifampicin. This can lead to antiretroviral drugs become ineffective, tuberculosis treatment ineffective, or an increased risk of drug toxicity.
- Interaction with Laboratorium tests :
- Cross-reactivity and false-positive urine screening tests for Opioids have been reported in patients receiving Rifampicin with the use of KIMS (Kinetic Interaction of Microparticles in Solution) as Abuscreen Online Opiates Assay; Roche Diagnostic System. Gas chromatography or mass spectrometry confirmation test, will distinguish Rifampicin from Opioids.
- Therapeutic level of Rifampicin inhibits the standard microbiological testing for Folat Serum and Vitamin B12, therefore alternative testing methods need to be considered. Liver function tests such as an increase in bilirubin serum, alkaline phospatase, serum transaminase and reduction of gall bladder excretion from contrast media used for visualization of the gall bladder should be performed before the morning dose of Rifampicin, as has been observed occurrence of abnormalities while on the test.
ADVERSE REACTIONS :
- Liver disorder :
Rifampicin side effects reaction that most important is hepatotoxicity, particularly cholestatic reactions and skin reactions. Rifampicin can cause sub-clinical hiperbilirubin unconjugated, or jaundice without damage to the liver cells, but it can cause injury at the liver cell. Rifampicin can also increase hepatotoxicity effects of other anti tuberculosis drugs.
- Very common : Transient increase of transaminase serum.
- Uncommon : Increased bilirubin serum and alkaline phospatase, hepatitis.
- Digestive disorder :
- Very common : Diarrhea, abdominal pain, nausea, anorexia and vomiting.
- Rarely : Erosive gastritis, colitis pseudo-membranous.
- Frequency not known : Dry mouth, flatulence and constipation.
- Blood and lymphatic system disorders :
Frequency not known : Anemia (hemolytic, sideroblastic, or aplastic), thrombocytopenia, leucopenia, neutropenia with eosinophilia and agranulocytosis.
- Central nervous system disorder :
Headache, fatigue, drowsiness, ataxia, dizziness, difficulty concentrating, confusion, behavioral changes, muscle weakness, pain in the limbs and numbness have been observed. Psychosis and myopathy rarely reported.
- Eye disorder :
- General : Eye redness, permanent discoloration of contact lenses.
- Rare : Exudative conjunctivitis.
- Frequency not known : Optic atrophy or neuritis.
- Endocrine disorder :
- Menstrual disorders have been reported.
- Adrenal insufficiency in patients rarely reported.
- Renal and urinary disorders :
- Rarely : Acute renal failure, interstitial nephritis, hemolysis, hemoglobinuria, hematuria, acute tubular necrosis, renal insufficiency.
- Frequency not known : Urinary retention.
- Skin and sub-cutaneous tissues disorder :
- Common : Erythema, exanthema, pruritus with or without rash, urticaria.
- Rarely : Photosensitivity reactions, exfoliative dermatitis, pemphigoid reaction and purpura.
- Frequency not known : Lyell Syndrome, Steven-Johnson Syndrome.
- Hypersensitivity reactions :
Sometimes pruritus, urticaria, rash, pemphigoid reaction, erythema multiforme, including toxic epidermal necrolysis, vasculitis, eosinophilia and anaphylaxis (rarely reported) can occur.
- Others :
Edema of the face and limbs has been reported. Other reactions that have been reported in the treatment of intermittent include “flu syndrome” (fever, chills, headache, dizziness and bone pain), difficulty breathing, wheezing, decrease in blood pressure and shock.
PRESENTATIONS :
Rifampicin Film coated caplet 600 mg Box, 10 strips @ 10 film coated caplets
Reg. No. GKL9302317709B1
STORAGE :
STORE BELOW 30ºC, PROTECT FROM LIGHT
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
