Active ingredients: Rifampicin
RIFADIN 150 mg hard capsules
RIFADIN 300 mg hard capsules
RIFADIN 450 mg coated tablets
RIFADIN 600 mg coated tablets
RIFADIN 20 mg / ml syrup
RIFADIN 600 mg / 10 ml powder and solvent for solution for infusion
Why is Rifadin used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antimicobacterials, antibiotics.
THERAPEUTIC INDICATIONS
Infections with rifampicin-sensitive microorganisms and in particular with tuberculous mycobacterium and other mycobacteria. In mycobacterial infections, use in combination with other specific antibiotics or chemotherapeutic agents is mandatory. In non-tuberculous infections, the association of another active antibiotic is recommended, to avoid any onset of resistance. The sensitivity of pathogens, or their possible primary or acquired resistance, should be determined by means of an antibiogram, similarly to what is generally expected for a correct use of antibiotics.
In the event that the infection does not respond within a reasonable period of time, the treatment will have to be changed, and in the event of a relapse it is not recommended to administer rifampicin without having carried out preliminary bacteriological tests.
Contraindications When Rifadin should not be used
Rifadin must not be administered to patients with hypersensitivity to the active substance or to any of the excipients and in case of jaundice.
The use of Rifadin is contraindicated when used concomitantly with the combination saquinavir / ritonavir (see section Interactions).
Precautions for use What you need to know before taking Rifadin
Adults treated with Rifadin should have initial check of liver enzymes, bilirubin, serum creatinine, complete blood count and platelets. In children, this initial check-up is not necessary except in the presence of a known or suspected condition that can cause complications.
Patients should be seen at least every month and specific information on symptoms related to undesirable effects should be requested. All patients with any type of abnormal data should be followed up, even with laboratory checks, if necessary.
Rifadin has enzyme inducing properties and may increase the metabolism of endogenous substrates including adrenal, thyroid hormones and vitamin D. Isolated reports have associated administration of Rifadin with exacerbation of porphyria, as a consequence of the induction of delta amino acid synthetase levulinic.
Rifadin may cause a reddish discoloration of urine, sweat, sputum and tears. Patients should be advised of this.
Soft contact lenses were permanently colored.
Rifadin solution in vial is for intravenous infusion only and must not be administered intramuscularly or subcutaneously. It is advisable to avoid the escape of the solution from the vascular site during the injection; cases of local irritation and inflammation due to extravascular infiltration of the infused solution have been observed. If these reactions occur, the infusion must be suspended and carried out at another site .
Interactions Which drugs or foods can modify the effect of Rifadin
Interactions with cytochrome P-450 enzymes
Rifadin is a potent inducer of some cytochrome P-450 enzymes. Co-administration of Rifadin with other drugs also metabolised through these cytochrome P-450 enzymes may increase the elimination and decrease the activity of these other drugs. Therefore, caution is required when administering Rifadin with drugs metabolised by cytochrome P - 450. At the start of treatment with Rifadin or when it is stopped, it may be necessary to adjust the dosage of drugs metabolised by these enzymes, to maintain therapeutically optimal plasma concentrations.
Examples of drugs metabolized by cytochrome P-450 enzymes are:
- anticonvulsants (e.g. phenytoin)
- antiarrhythmics (e.g. disopyramide, mexiletine, quinidine, propafenone, tocainide)
- antiestrogens (e.g. tamoxifen, toremifene)
- antipsychotics (e.g. haloperidol)
- oral anticoagulants (e.g. warfarin)
- tricyclic antidepressants (e.g. amitriptyline, nortriptyline)
- antifungals (e.g. fluconazole, itraconazole, ketoconazole)
- antiretrovirals (e.g. zidovudine, saquinavir, indinavir, efavirenz) - barbiturates
- beta blockers
- benzodiazepines (e.g. diazepam)
- calcium channel blockers (e.g. diltiazem, nifedipine, verapamil)
- chloramphenicol
- clarithromycin
- corticosteroids
- clofibrate
- oral contraceptives
- dapsone
- doxycycline
- estrogen
- benzodiazepine-like drugs (e.g. zopiclone, zolpidem)
- fluoroquinolones
- gestrinone
- cardiac glycosides
- immunosuppressants (e.g. cyclosporine, tacrolimus)
- oral hypoglycemic agents (e.g. sulfonylureas)
- irinotecan
- levothyroxine
- losartan
- narcotic analgesics
- methadone
- praziquantel
- progestogens, quinine
- riluzole
- 5-HT3 selective antagonists (e.g. ondansetron)
- statins metabolised by CYP 3A4
- telithromycin
- theophylline
- thiazolidinediones (e.g. rosiglitazone)
Patients on oral contraceptive therapy should use non-hormonal methods of contraception during Rifadin therapy.
Other interactions
When Rifadin is administered concomitantly with the saquinavir / ritonavir combination, it increases the potential hepatotoxicity. Therefore, the concomitant use of Rifadin with saquinavir / ritonavir is contraindicated (see section Contraindications).
Reduced concentrations of the former and increased concentrations of the latter were observed with concomitant administration of atovaquone and rifampicin.
Concomitant use of ketoconazole and Rifadin resulted in decreased serum levels of both drugs.
Concomitant use of enalapril and Rifadin resulted in increased levels of enalaprilat, the active metabolite of enalapril. If the patient's clinical condition requires it, dose adjustments should be made
The concomitant intake of antacids can reduce the absorption of Rifadin. The daily administration of Rifadin should be done at least 1 hour before the intake of antacids.
The potential for hepatotoxicity is increased with concomitant administration of halothane or isoniazid.
The concomitant use of Rifadin and halothane should be avoided. Patients receiving Rifadin and isoniazid should be carefully monitored for possible hepatotoxicity. Simultaneous administration of para-aminosalicylic acid (PAS) in formulations containing bentonite as an excipient, and rifampicin can induce a reduction in the blood levels of the latter. The two drugs must be administered with an interval of at least 8 hours.
Interference with diagnostic and laboratory tests
Therapeutic levels of Rifadin have been shown to inhibit standard microbiological tests for folate and Vitamin B12. Therefore alternative tests must be used.
A transient increase in serum bilirubin levels was also observed (see Warnings section). Rifadin may reduce biliary excretion of contrast media used for gallbladder visualization, due to competition for biliary excretion. Therefore such tests should be done before taking the morning dose of Rifadin.
Using the Kinetic Interaction of Microparticles in Solution (KIMS) method, cross-reactivity and false positives have been reported in urinary tests for the determination of opiates performed in patients receiving rifampicin. Gas chromatography and mass spectrometry, used as confirmatory tests, are able to distinguish rifampicin from opiates.
Warnings It is important to know that:
In the treatment of non-tuberculous infections, if an associated tuberculous form is suspected, Rifadin should not be used before the diagnosis is clarified, in order not to mask the tuberculous process and not to cause the onset of mycobacterial resistance.
In poorly nourished elderly subjects and in early childhood, particular caution should be exercised especially in the case of simultaneous administration of isoniazid.
Liver
In patients with impaired hepatic function Rifadin should only be administered when necessary, with caution and under careful medical supervision. In these patients, careful monitoring of liver function, particularly serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), should be performed prior to initiation of therapy and thereafter at 2-4 week intervals. If signs develop. of hepatocellular damage, Rifadin must be discontinued.
In some cases, hyperbilirubinemia may occur in the first days of therapy, as a consequence of a competition between Rifadin and bilirubin on the processes of excretion of hepatocytes. An isolated, moderate increase in bilirubin and / or transaminases does not in itself constitute a reason for discontinuing therapy; the decision must be made after repetition of the checks confirming the tendency to increase the values and taking into consideration the clinical condition of the patient.
Immunological reactions / anaphylaxis
Since there is a potential for immunological reactions, including anaphylaxis, including anaphylaxis (see section Undesirable effects), with intermittent regimens (less than 2 - 3 times per week), patients should be followed closely. Patients should be advised not to discontinue therapy as these events may occur.
Rifadin Syrup
Rifadin syrup contains sucrose so if you have been informed that you have an "intolerance to some sugars, contact your doctor before taking this medicine.
Rifadin syrup contains sodium metabisulfite which, in some sensitive patients, can cause allergic-type reactions, including anaphylactic symptoms and asthma attacks which can also be life-threatening.
The syrup also contains p-hydroxybenzoates which can cause allergic reactions.
Rifadin coated tablets
Rifadin tablets contain lactose and sucrose so if you have been informed that you have an "intolerance to some sugars, contact your doctor before taking this medicine.
Pregnancy and breastfeeding
There are no well-controlled studies on the use of rifampicin in pregnant women.
High doses of rifampicin were found to be teratogenic in rodents.
Although Rifadin has been reported to cross the placenta and is present in cord blood, the effect of the drug on the fetus, alone or in combination with other anti-tuberculosis drugs, is not known.
When rifampicin is administered in the last weeks of pregnancy it can cause postnatal haemorrhages in the mother and newborn, which may require the use of vitamin K.
Therefore, in pregnant women or women of childbearing potential, the antibiotic should only be used if the potential benefit justifies the potential risk to the fetus.
There are no data on the long-term effect on human fertility.
Rifampicin is excreted in breast milk so the antibiotic should only be used during breastfeeding if the potential benefit justifies the potential risk to the baby.
Effects on ability to drive and use machines
There is no known interference with the ability to drive and use machines.
Dosage and method of use How to use Rifadin: Dosage
Oral Rifadin
Adults: in tuberculosis 600 mg per day in a single administration for patients over 50 kg in weight (450 mg for patients under 50 kg in weight), combined with other anti-tuberculosis drugs. In other infections the daily dose can reach 900-1200 mg, usually divided into two administrations.
Children: the recommended daily dose is 10-20 mg / kg of body weight divided into two equal doses. It is recommended not to exceed the daily dose of 600 mg.
Shake the bottle well and gently before use, avoiding the formation of foam.
It is advisable to wash the glass well with water after each syrup withdrawal.
Instructions for use: for a more rapid and complete absorption it is advisable to administer Rifadin on an empty stomach, away from meals (at least 30 minutes before a meal or 2 hours after a meal).
In the cases of initial assessment, the most effective treatment is the continuous one of reduced duration, ie nine months, with the aforementioned doses, combined with isoniazid and, in the first three months, with a third anti-tuberculosis.
Rifadin solution for infusion
Rifadin is available in vial (containing 600 mg of antibiotic) with solvent ampoule. Rifadin for intravenous infusion is particularly recommended when the clinical situation (surgery, impaired gastrointestinal absorption, etc.) or the patient's gastric tolerability conditions do not allow or do not recommend the administration of the antibiotic by mouth.
The solution is prepared by introducing the solvent from the vial enclosed in the package into the rifampicin powder vial and shaking vigorously and without interruption for about 30 seconds.
Once the foam has completely disappeared, this solution must be immediately diluted in 500 ml of 5% glucose solution or physiological saline. The preparation thus prepared must be used within a few hours. It is advisable to adjust the drip speed so that the infusion lasts about 3 hours.
Posology in non-specific infections: in adults the suggested daily dose is 600 mg (in the opinion of the physician: one vial of 600 mg once a day).
Posology in pulmonary tuberculosis: in adults the suggested daily dose is 600 mg, generally in a single administration. Treatment of pulmonary tuberculosis with Rifadin by intravenous infusion should include the simultaneous use of other anti-tuberculous drugs.
In case of failure to administer one or more doses, consult the doctor who made the prescription before resuming therapy, for the correct restoration of the therapeutic scheme.
Overdose What to do if you have taken too much Rifadin
Signs and symptoms
Nausea, vomiting, abdominal pain, itching, headache and increased lethargy may occur within a short time after acute administration; in case of severe liver disease there may be loss of consciousness. Transient increases in liver enzymes and / or bilirubin may occur. A reddish-brown or orange discoloration of the skin, urine, sweat, saliva, tears and faeces occurs, the intensity of which is proportional to the dose taken. Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, convulsions and cardiac arrest have been reported in some fatal cases.
The minimal lethal or acute toxic dose is unknown. However, there have been reports of acute non-lethal overdose in adults taking 9-12 g of rifampicin. Acute lethal overdoses have been observed in adults following the intake of 4/5 doses ranging from 14 to 60 g. In some cases, both lethal and non-lethal, there was a history of alcohol consumption or abuse.
Non-lethal overdoses have been reported in pediatric patients aged 1 to 4 years treated with doses of 100 mg / kg (1 or 2 doses).
Treatment
Intensive supportive measures should be taken and symptoms treated as they occur. Since nausea and vomiting are likely to be present, gastric lavage is preferable to induction of emesis. After emptying the gastric contents, instillation of activated charcoal into the stomach can aid in the absorption of residual drug into the gastrointestinal tract. antiemetic therapy in case of severe nausea and vomiting. Active diuresis (with control of intake and elimination) will promote the excretion of the drug. In some patients, hemodialysis may be useful.
Side Effects What are the side effects of Rifadin
Mild skin reactions may occur which do not appear to be allergic in nature. They usually consist of redness and itching with or without the appearance of a rash. More severe hives and skin reactions of hypersensitivity have occurred but are not common. Cases of pemphigoid reaction, erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis and vasculitis have been reported rarely.
Gastrointestinal disturbances such as anorexia, nausea, vomiting, abdominal discomfort and diarrhea have been reported. Pseudomembranous colitis has been reported with Rifadin.
Rifadin can cause hepatitis and therefore liver function tests should be performed (see section Special warnings).
Central nervous system: Psychosis has rarely been reported.
Thrombocytopenia with or without purpura may occur, usually associated with intermittent therapy but is reversible if therapy is stopped promptly upon the appearance of purpura.
Cerebral haemorrhage and fatal events have been reported following continued use or reintroduction of the drug after the onset of purpura. Disseminated intravascular coagulation has rarely been reported.
Eosinophilia, leukopenia, edema, muscle weakness and myopathy have been reported in a small percentage of patients receiving Rifadin.
Agranulocytosis has been reported very rarely.
There have been rare cases of adrenal insufficiency in patients with impaired adrenal function.
Menstrual disturbances have been reported in women undergoing long-term antituberculosis therapy with rifampicin-containing regimens.
Reactions that usually occur with intermittent regimens, possibly of immunological origin, include: "flu syndrome" with febrile episodes, chills, headache, dizziness and bone pain; wheezing and wheezing; drop in blood pressure and shock; anaphylaxis; acute hemolytic anemia; acute renal failure due to acute tubular necrosis or acute interstitial nephritis.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
It is important to inform the doctor or pharmacist of any undesirable effect, even if not described in the package leaflet.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Conservation: None
RIFADIN 600 mg / 10 ml powder and solvent for solution for infusion
Storage: Do not store above 25 ° C.
RIFADIN 450 mg coated tablets
RIFADIN 600 mg coated tablets
RIFADIN 20 mg / ml syrup
RIFADIN 150 mg hard capsules
RIFADIN 300 mg hard capsules
WARNING: do not use the medicine after the expiry date indicated on the package.
Keep out of the reach and sight of children
COMPOSITION
Rifadin 150 mg hard capsules
One capsule contains:
Active principle: rifampicin 150 mg
Exciipents: corn starch, magnesium stearate, gelatin, erythrosine (E 127), indigo carmine (E 132), titanium dioxide (E 171).
Rifadin 300 mg hard capsules
One capsule contains:
Active principle: rifampicin 300 mg
Excipients: corn starch, magnesium stearate, gelatin, erythrosine (E 127), indigo carmine (E 132), titanium dioxide (E 171).
Rifadin 450 mg coated tablets
One tablet contains:
Active principle: rifampicin 450 mg
Excipients: sodium lauryl sulfate, microgranular cellulose, lactose, calcium stearate, carmellose sodium, corn starch, gum arabic, povidone, sucrose, talc, magnesium carbonate, titanium dioxide (E 171), kaolin, colloidal silica, erythrosine (E 127) aluminum lake 17%, magnesium stearate, gelatin.
Rifadin 600 mg coated tablets
One tablet contains:
Active principle: rifampicin 600 mg
Excipients: sodium lauryl sulfate, microgranular cellulose, lactose, calcium stearate, carmellose sodium, corn starch, gum arabic, povidone, sucrose, talc, magnesium carbonate, titanium dioxide (E 171), kaolin, colloidal silica, erythrosine (E 127) aluminum lake 17%, magnesium stearate, gelatin.
Rifadin 20 mg / ml syrup
100 ml of suspension contain:
Active principle: rifampicin 2 g.
Excipients: agar-agar, sucrose, potassium sorbate, saccharin, methyl parahydroxybenzoate, propyl parahydroxybenzoate, sodium metabisulphite, polysorbate 80, raspberry essence, diethanolamine, purified water.
Rifadin 600 mg / 10ml powder and solvent for solution for infusion
One powder vial contains:
Active principle: rifampicin 600 mg.
Excipients: sodium formaldehyde sulfoxylate, sodium hydroxide. One ampoule of solvent contains: water for injections.
PHARMACEUTICAL FORMS AND CONTENT
Hard capsules:
Rifadin 150 mg hard capsules: 8 capsules
Rifadin 300 mg hard capsules: 8 capsules
Coated tablets:
Rifadin 450 mg coated tablets: 8 tablets
Rifadin 600 mg coated tablets: 8 tablets
Syrup: 60 ml bottle with graduated measuring cup
Powder and solvent for solution for infusion: 1 vial of powder + 1 vial of 10 ml solvent.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
RIFADIN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Rifadin 150 mg hard capsules
One capsule contains:
Active principle: rifampicin 150 mg.
Rifadin 300 mg hard capsules
One capsule contains:
Active principle: rifampicin 300 mg.
Rifadin 450 mg coated tablets
One tablet contains:
Active principle: rifampicin 450 mg.
Rifadin 600 mg coated tablets
One tablet contains:
Active principle: rifampicin 600 mg.
Rifadin 20 mg / ml syrup
100 ml of suspension contain:
Active principle: rifampicin 2 g.
Rifadin 600 mg / 10 ml powder and solvent for solution for infusion
One powder vial contains:
Active principle: rifampicin 600 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsules, coated tablets, syrup, powder and solvent for solution for infusion.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Infections with rifampicin-sensitive microorganisms and in particular with tuberculous mycobacterium and other mycobacteria. In mycobacterial infections, use in combination with other specific antibiotics or chemotherapeutic agents is mandatory. In non-tuberculous infections, the association of another active antibiotic is recommended, to avoid any onset of resistance. The sensitivity of pathogens, or their possible primary or acquired resistance, should be determined by means of an antibiogram, similarly to what is generally expected for a correct use of antibiotics.
In the event that the infection does not respond within a reasonable period of time, the treatment will have to be changed, and in the event of a relapse it is not recommended to administer rifampicin without having carried out preliminary bacteriological tests.
04.2 Posology and method of administration
Oral Rifadin
Adults: in tuberculosis 600 mg per day in a single administration for patients over 50 kg in weight (450 mg for patients under 50 kg in weight), associated with other anti-tuberculosis drugs. In other infections the daily dose can reach 900-1200 mg, usually divided into two administrations.
Children: the recommended daily dose is 10-20 mg / kg of body weight divided into two equal doses. It is recommended not to exceed the daily dose of 600 mg.
Shake the bottle well and gently before use, avoiding the formation of foam.
It is advisable to wash the glass well with water after each syrup withdrawal.
Rules for use: for a more rapid and complete absorption it is recommended to administer Rifadin on an empty stomach, away from meals (at least 30 minutes before a meal or 2 hours after a meal).
In the cases of initial assessment, the most effective treatment is the continuous treatment of reduced duration, ie nine months, with the aforementioned doses, associated with isoniazid and in the first three months with a third anti-tuberculosis.
Rifadin solution for infusion
Rifadin is available in a vial (containing 600 mg of antibiotic) with a solvent ampoule. Rifadin for intravenous infusion is particularly recommended when the clinical situation (surgery, impaired gastrointestinal absorption, etc.) or the patient's gastric tolerability conditions do not allow or do not recommend the administration of the antibiotic by mouth.
The solution is prepared by introducing the solvent from the vial enclosed in the package into the rifampicin vial and shaking vigorously and without interruption for about 30 seconds.
Once the foam has completely disappeared, this solution must be immediately diluted in 500 ml of 5% glucose solution or physiological saline. The preparation thus prepared must be used within a few hours. It is advisable to adjust the drip speed so that the infusion lasts about 3 hours.
Posology in non-specific infections: in adults, the recommended daily dose is 600 mg (in the opinion of the doctor: one vial of 600 mg once a day).
Posology in pulmonary tuberculosis: in adults the suggested daily dose is 600 mg, generally in a single administration. Treatment of pulmonary TB with Rifadin by intravenous infusion should include the simultaneous use of other anti-tuberculosis drugs.
04.3 Contraindications
Rifadin must not be administered to patients with hypersensitivity to the active substance or to any of the excipients and in case of jaundice.
The use of Rifadin is contraindicated when used concomitantly with the combination saquinavir / ritonavir (see section 4.5).
04.4 Special warnings and appropriate precautions for use
In the treatment of non-tuberculous infections, if an associated tuberculous form is suspected, Rifadin should not be used before the diagnosis is clarified, in order not to mask the tuberculous process and not to cause the onset of mycobacterial resistance.
In poorly nourished elderly subjects and in early childhood, particular caution should be exercised especially in the case of simultaneous administration of isoniazid.
Liver
In patients with impaired hepatic function Rifadin should only be administered when necessary, with caution and under careful medical supervision. In these patients, careful monitoring of liver function, particularly serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), should be performed prior to initiation of therapy and thereafter at 2-4 week intervals. If signs develop. of hepatocellular damage, Rifadin must be discontinued.
In some cases, hyperbilirubinemia may occur in the first days of therapy, as a consequence of a competition between Rifadin and bilirubin on the processes of excretion of hepatocytes. An isolated, moderate increase in bilirubin and / or transaminases does not in itself constitute a reason for discontinuing therapy; the decision must be made after repetition of the checks confirming the tendency to increase the values and taking into consideration the clinical condition of the patient.
Immunological reactions / anaphylaxis
Since there is a potential for immunological reactions, including anaphylaxis, including anaphylaxis (see section 4.8) with intermittent regimens (less than 2 to 3 times per week), patients should be followed closely. Patients should be advised not to discontinue therapy as these events may occur.
Rifadin Syrup
Rifadin syrup contains sucrose and is therefore not suitable for individuals with hereditary fructose intolerance, glucose / galactose malabsorption syndrome or sucrase-isomaltase deficiency.
Rifadin syrup contains sodium metabisulfite which, in some sensitive patients, can cause allergic-type reactions, including anaphylactic symptoms and asthma attacks which can also be life-threatening.
The syrup also contains p-hydroxybenzoates which can cause allergic reactions.
Rifadin coated tablets
Rifadin tablets contain lactose and therefore patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Rifadin tablets contain sucrose and are therefore not suitable for people with hereditary fructose intolerance, glucose / galactose malabsorption syndrome or sucrase-isomaltase deficiency.
Precautions
Adults treated with Rifadin should have initial check of liver enzymes, bilirubin, serum creatinine, monochromes and platelets. In children, this initial check-up is not necessary except in the presence of a known or suspected condition that can cause complications.
Patients should be seen at least every month and specific information on symptoms related to undesirable effects should be requested. All patients with any type of abnormal data should be followed up, even with laboratory checks, if necessary.
Rifadin has enzyme inducing properties and may increase the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D. Isolated reports have associated administration of Rifadin with exacerbation of porphyria, as a consequence of the induction of delta amino acid sitetase levulinic.
Rifadin may cause a reddish discoloration of urine, sweat, sputum and tears. Patients should be advised of this.
Soft contact lenses were permanently colored.
Rifadin solution in vial is for intravenous infusion only and must not be administered intramuscularly or subcutaneously. It is advisable to avoid the escape of the solution from the vascular site during the injection; cases of local irritation and inflammation due to extravascular infiltration of the infused solution have been observed. If these reactions occur, the infusion must be suspended and carried out at another site .
Keep out of the reach and sight of children.
04.5 Interactions with other medicinal products and other forms of interaction
Interactions with cytochrome P-450 enzymes
Rifadin is a potent inducer of some cytochrome P-450 enzymes. Co-administration of Rifadin with other drugs also metabolised through these cytochrome P-450 enzymes may increase the elimination and decrease the activity of these other drugs. Therefore, caution is required when administering Rifadin with drugs metabolised by cytochrome P -450 At the start of treatment with Rifadin or when it is stopped, it may be necessary to adjust the dosage of drugs metabolised by these enzymes to maintain therapeutically optimal plasma concentrations.
Examples of drugs metabolized by cytochrome P-450 enzymes are:
- anticonvulsants (e.g. phenytoin)
- antiarrhythmics (e.g. disopyramide, mexiletine, quinidine, propafenone, tocainide)
- antiestrogens (e.g. tamoxifen, toremifene)
- antipsychotics (e.g. haloperidol)
- oral anticoagulants (e.g. warfarin)
- tricyclic antidepressants (e.g. amitriptyline, nortriptyline)
- antifungals (e.g. fluconazole, itraconazole, ketoconazole)
- antiretrovirals (e.g. zidovudine, saquinavir, indinavir, efavirenz)
- barbiturates
- beta blockers
- benzodiazepines (e.g. diazepam)
- calcium channel blockers (e.g. diltiazem, nifedipine, verapamil)
- chloramphenicol
- clarithromycin
- corticosteroids
- clofibrate
- oral contraceptives
- dapsone
- doxycycline
- estrogen
- benzodiazepine-like drugs (e.g. zopiclone, zolpidem)
- fluoroquinolones
- gestrinone
- cardioactive glycosides
- immunosuppressants (e.g. cyclosporine, tacrolimus)
- oral hypoglycemic agents (e.g. sulfonylureas)
- irinotecan
- levothyroxine
- losartan
- narcotic analgesics
- methadone
- praziquantel
- progestogens, quinine
- riluzole
- 5-HT3 selective antagonists (e.g. ondansetron)
- statins metabolised by CYP 3A4
- telithromycin
- theophylline
- thiazolidinediones (e.g. rosiglitazone)
Patients on oral contraceptive therapy should use non-hormonal methods of contraception during Rifadin therapy.
Other interactions
When Rifadin is administered concomitantly with the saquinavir / ritonavir combination, it increases the potential hepatotoxicity. Therefore, the concomitant use of Rifadin with saquinavir / ritonavir is contraindicated (see section 4.3).
Reduced concentrations of the former and increased concentrations of the latter were observed with concomitant administration of atovaquone and rifampicin.
Concomitant use of ketoconazole and Rifadin resulted in decreased serum levels of both drugs.
Concomitant use of enalapril and Rifadin resulted in increased levels of enalaprilat, the active metabolite of enalapril. If the patient's clinical condition requires it, dose adjustments should be made.
The concomitant intake of antacids can reduce the absorption of Rifadin. The daily administration of Rifadin should be done at least 1 hour before the intake of antacids.
The potential for hepatotoxicity is increased with concomitant administration of halothane or isoniazid. The concomitant use of Rifadin and halothane should be avoided. Patients receiving Rifadin and isoniazid should be monitored closely for possible hepatotoxicity.
The simultaneous administration of para-aminosalicylic acid (P.A.S.) in formulations containing bentonite as excipient, and rifampicin can induce a reduction in the blood levels of the latter. The two drugs must be administered with an interval of at least 8 hours.
Interference with diagnostic and laboratory tests
Therapeutic levels of Rifadin have been shown to inhibit standard microbiological tests for folate and Vitamin B12. Therefore alternative tests must be used. A transient increase in serum bilirubin levels was also observed (see section 4.4). Rifadin may reduce biliary excretion of contrast media used for gallbladder visualization, due to competition for biliary excretion. Therefore such tests should be done before taking the morning dose of Rifadin.
Using the Kinetic Interaction of Microparticles in Solution (KIMS) method, cross-reactivity and false positives have been reported in urinary tests for the determination of opiates performed in patients receiving rifampicin. Gas chromatography and mass spectrometry, used as confirmatory tests, are able to distinguish rifampicin from opiates.
04.6 Pregnancy and lactation
There are no well-controlled studies on the use of rifampicin in pregnant women.
High doses of rifampicin were found to be teratogenic in rodents.
Although Rifadin has been reported to cross the placenta and is present in cord blood, the effect does on the fetus of the drug, alone or in combination with other anti-tuberculosis drugs, is not known.
When rifampicin is administered in the last weeks of pregnancy it can cause postnatal haemorrhages in the mother and newborn, which may require the use of vitamin K.
Therefore, in pregnant women or women of childbearing potential, the antibiotic should only be used if the potential benefit justifies the potential risk to the fetus.
There are no data on the long-term effect on human fertility.
Rifampicin is excreted in breast milk so the antibiotic should only be used during breastfeeding if the potential benefit justifies the potential risk to the baby.
04.7 Effects on ability to drive and use machines
There is no known interference with the ability to drive and use machines.
04.8 Undesirable effects
Mild skin reactions may occur which do not appear to be allergic in nature. They usually consist of redness and itching with or without the appearance of a rash. More severe hives and skin reactions of hypersensitivity have occurred but are not common. Cases of pemphigoid reaction, erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis and vasculitis have been reported rarely.
Gastrointestinal disturbances such as anorexia, nausea, vomiting, abdominal discomfort and diarrhea have been reported. Pseudomembranous colitis has been reported with Rifadin.
Rifadin can cause hepatitis and therefore liver function tests should be performed (see section 4.4).
Central nervous system: Psychosis has rarely been reported.
Thrombocytopenia with or without purpura may occur, usually associated with intermittent therapy but is reversible if therapy is stopped promptly upon the appearance of purpura. Cerebral haemorrhage and fatal events have been reported following continued use or reintroduction of the drug after the onset of purpura.
Disseminated intravascular coagulation has rarely been reported.
Eosinophilia, leukopenia, edema, muscle weakness and myopathy have been reported in a small percentage of patients receiving Rifadin.
Agranulocytosis has been reported very rarely.
There have been rare cases of adrenal insufficiency in patients with impaired adrenal function.
Menstrual disturbances have been reported in women undergoing long-term antituberculosis therapy with rifampicin-containing regimens.
Reactions that usually occur with intermittent regimens, possibly of immunological origin, include: "flu syndrome" with febrile episodes, chills, headache, dizziness and bone pain; wheezing and wheezing; drop in blood pressure and shock; anaphylaxis; acute hemolytic anemia; acute renal failure due to acute tubular necrosis or acute interstitial nephritis.
04.9 Overdose
Signs and symptoms
Nausea, vomiting, abdominal pain, itching, headache and increased lethargy may occur within a short time after acute administration; in case of severe liver disease there may be loss of consciousness. Transient increases in liver enzymes and / or bilirubin may occur. A reddish-brown or orange discoloration of the skin, urine, sweat, saliva, tears and faeces occurs, the intensity of which is proportional to the dose taken. Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, convulsions and cardiac arrest have been reported in some fatal cases.
The minimal lethal or acute toxic dose is unknown. However, there have been reports of acute non-lethal overdose in adults taking 9-12 g of rifampicin. Acute lethal overdoses have been observed in adults following the intake of doses between 14 and 60 g. In some cases, both lethal and non-lethal, there was a history of alcohol consumption or abuse.
Non-lethal overdoses have been reported in pediatric patients aged 1 to 4 years treated with doses of 100 mg / kg (1 or 2 doses).
Treatment
Intensive supportive measures should be taken and symptoms treated as they occur. Since nausea and vomiting are likely to be present, gastric lavage is preferable to induction of emesis. After emptying the gastric contents, instillation of activated charcoal into the stomach can aid in the absorption of residual drug into the gastrointestinal tract. antiemetic therapy in case of severe nausea and vomiting. Active diuresis (with control of intake and elimination) will promote the excretion of the drug. In some patients, hemodialysis may be useful.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antimcobacterials, antibiotics.
ATC code: J04AB02.
Rifadin inhibits the activity of DNA-dependent RNA polymerase in sensitive cells. More specifically, it interacts with bacterial RNA polymerase but does not inhibit the enzyme in mammals.
Rifadin is particularly active against rapidly growing extracellular microorganisms but also possesses intracellular antibacterial activity againstM. tuberculosis slow-growing and intermittent.
It is also active in vitro against Mycobacterium avium Complex, M. kansasii And M. leprae.
Rifadin is active in vitro against a range of gram-positive and gram-negative microorganisms. Sensitive microorganisms include Neisseria meningitidis, Neisseria gonorrhoeae, Staphylococcus aureus, Proteus spp, Staphylococcus epidermidis, H. influenzae, E. coli, Ps. aeruginosa, Legionella pneumophila, Brucella spp. And Streptococcus pyogenes. Staphylococci that produce both penicillinase and non-penicillinase and those resistant to beta-lactams are sensitive to Rifadin.
Cross-resistance with rifampicin has only been demonstrated with other rifamycins.
05.2 Pharmacokinetic properties
Oral rifadin is rapidly absorbed from the gastrointestinal tract. Peak plasma levels in adults and children vary widely from person to person. Peak serum concentrations of approximately 10 mcg / mL occur 2 to 4 hours after oral intake of an empty stomach dose of 10 mg / kg body weight. The absorption of Rifadin is reduced by the presence of food.
After intravenous administration of doses of 300 and 600 mg as a 30-minute infusion to healthy male volunteers (n = 12), peak plasma concentrations of 9.0 and 17.5 mcg / ml, respectively, were achieved. The mean plasma rate in these volunteers remained detectable for 8 and 12 hours, respectively.
Pharmacokinetics (oral and intravenous) in children are similar to that in adults.
In normal subjects the biological half-life of Rifadin in serum is about 3 hours after administration of 600 mg and increases to 5.1 hours with a dose of 900 mg. With repeated administration the half-life decreases and reaches mean values of about 2- 3 hours.
At a dose of 600 mg / day the half-life is similar in patients with renal insufficiency and therefore no dosage adjustments are necessary.
After absorption Rifadin (oral or i.v.) is rapidly eliminated in the bile and an enterohepatic circulation is established. During this phase Rifadin is progressively deacetylated so that almost all the share in the bile is acetylated within 6 hours. This metabolite maintains antibacterial activity.
Intestinal reabsorption is reduced by acetylation and thus facilitated elimination. About 30% of the dose is excreted in the urine of which about half in unchanged form. Rifadin is widely distributed throughout the body. It is present in effective concentrations in many organs and fluids including the cerebrospinal fluid.
Rifadin is 80% bound to plasma proteins. Most of the unbound portion is in non-ionized form and therefore easily diffuses to tissues.
05.3 Preclinical safety data
Carcinogenesis
There are no human data on the long-term potential for carcinogenicity. There have been some reports of worsening of human lung cancers, but a causal relationship with the drug has not been established. An increase in the incidence of hepatomas in female mice (of a type particularly sensitive to spontaneous development of hepatomas) was observed with the administration of Rifadin at doses of 2 to 10 times the mean human dose for 60 weeks, followed by an observation period of 46 weeks. There was no evidence of carcinogenicity in male mice of the same breed or in rats under similar experimental conditions.
Rifadin has been reported to have immunosuppressive potential in rabbits, mice, rats, guinea pigs, human lymphocytes in vitro and in humans.
Rifadin's antitumor activity has been demonstrated in vitro.
Mutagenesis
There are no human data on the long-term potential for mutagenesis. There was no evidence of mutagenesis in bacteria, Drosophila melanogaster or in mice. Increased chromatid breakdown was noted when human blood cell cultures were treated. In vitro an increased frequency of chromosomal aberrations was observed in lymphocytes obtained from patients treated with combinations of Rifadin, isoniazid and pyrazinamide and combinations of streptomycin, Rifadin, isoniazid and pyrazinamide.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Rifadin hard capsules
Corn starch, magnesium stearate, gelatin, erythrosine, indigo carmine, titanium dioxide.
Rifadin coated tablets
Sodium lauryl sulfate, microgranular cellulose, lactose, calcium stearate, carmellose sodium, corn starch, gum arabic, povidone, sucrose, talc, magnesium carbonate, titanium dioxide, kaolin, colloidal silica, erythrosine (E127) 17% aluminum lake, magnesium stearate , jelly.
Rifadin syrup
agar-agar; sucrose; potassium sorbate; saccharin; methyl parahydroxybenzoate; propyl parahydroxybenzoate; sodium metabisulfite; polysorbate 80; essence of raspberry; diethanolamine, purified water.
Rifadin powder and solvent for solution for infusion
One powder vial contains: sodium formaldehyde sulfoxylate; sodium hydroxide.
One solvent vial contains: water for injections.
06.2 Incompatibility
Physical incompatibility (formation of precipitates) was observed with simulated Y-site administration of diltiazem in undiluted (5 mg / ml) and diluted (1 mg / ml in normal saline) and rifampicin (6 mg / ml in normal saline) Rifadin solution for infusion must not be diluted in 1/6 mol sodium bicarbonate or sodium lactate solution as it may precipitate.
The use of 5% dextrose or normal saline is recommended for dilution of the reconstituted solution. The use of other infusion solutions is not recommended.
06.3 Period of validity
Hard capsules and coated tablets: 4 years.
Syrup: 3 years.
Powder and solvent for solution for infusion: 4 years.
06.4 Special precautions for storage
Conservation: None
RIFADIN 150 mg hard capsules
RIFADIN 600 mg / 10 ml powder and solvent for solution for infusion
Storage: Do not store above 25 ° C.
RIFADIN 450 mg coated tablets
RIFADIN 600 mg coated tablets
RIFADIN 20 mg / ml syrup
Storage: Do not store above 30 ° C.
RIFADIN 300 mg hard capsules
06.5 Nature of the immediate packaging and contents of the package
Carton containing capsules in blister packs:
"150 mg hard capsules" 8 capsules
"300 mg hard capsules" 8 capsules
Carton containing tablets in blister packs:
"450 mg coated tablets" 8 tablets
"600 mg coated tablets" 8 tablets
Carton containing "20 mg / ml syrup". 60 ml bottle with graduated measuring cup
Carton containing "600 mg / 10 ml powder and solvent for solution for infusion" 1 vial of powder + 1 vial of 10 ml solvent
06.6 Instructions for use and handling
The solution is prepared by introducing the water for injections from the solvent vial, included in the package, into the rifampicin powder vial and shaking gently until the antibiotic is completely dissolved. Once the foam has completely disappeared, this solution must be immediately diluted in 500 ml of 5% glucose solution or physiological saline. The preparation thus prepared must be used within a few hours. It is necessary to adjust the drip speed so that the infusion lasts about 3 hours.
07.0 MARKETING AUTHORIZATION HOLDER
sanofi-aventis S.p.A. - Viale L. Bodio, 37 / B - 20158 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Rifadin 150 mg hard capsules, 8 capsules AIC No. 021110200
Rifadin 300 mg hard capsules, 8 capsules AIC No. 021110034
Rifadin 450 mg coated tablets, 8 tablets AIC n. 021110097
Rifadin 600 mg coated tablets, 8 tablets AIC n. 021110111
Rifadin 20 mg / ml syrup, 60 ml bottle AIC n. 021110059
Rifadin 600 mg / 10 ml powder and solvent for solution for
infusion, 1 vial powder + 1 solvent vial of 10 ml AIC n. 021110135
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Rifadin 150 mg hard capsules, 8 capsules July 1968 / June 2010
Rifadin 300 mg hard capsules, 8 capsules July 1968 / June 2010
Rifadin 450 mg coated tablets, 8 tablets November 1978 / June 2010
Rifadin 600 mg coated tablets, 8 tablets November 1978 / June 2010
Rifadin 20 mg / ml syrup, 60 ml bottle June 1970 / June 2010
Rifadin 600 mg / 10 ml powder and solvent for solution for
infusion, 1 vial powder + 1 solvent vial of 10 ml November 1978 / June 2010
10.0 DATE OF REVISION OF THE TEXT
September 2013
