Human Experience
- Signs and Symptoms:
Nausea, vomiting, abdominal pain, pruritus, headache and increasing lethargy will probably occur within a short time after acute ingestion; unconsciousness may occur when there is severe hepatic disease. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange colouration of the skin, urine, sweat, saliva, tears and faeces will occur, and its intensity is proportional to the amount ingested. Facial or periorbital oedema has also been reported in paediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.
The minimum acute lethal or toxic dose is not well established. However, nonfatal acute overdoses in adults have been reported with doses ranging from 9 to 12 g rifampicin. Fatal acute overdoses in adults have been reported with doses ranging from 14-60 g. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal reports.
Nonfatal overdoses in paediatric patients ages 1 to 4 years old of 100 mg/kg for one to two doses have been reported.
- Management:
Intensive supportive measures should be instituted and individual symptoms treated as they arise. Since nausea and vomiting are likely to be present, gastric lavage is probably preferable to induction of emesis. Following evacuation of the gastric contents, the instillation of activated charcoal slurry into the stomach may help absorb any remaining drug from the gastrointestinal tract. Antiemetic medication may be required to control severe nausea and vomiting. Active diuresis (with measured intake and output) will help promote excretion of the drug. Haemodialysis may be of value in some patients.
3 years from date of manufacture
Rifadin is contra-indicated in the presence of jaundice, and in patients who are hypersensitive to the rifamycins or any of the excipients.
Rifadin use is contraindicated when given concurrently with the combination of saquinavir/ritonavir.
None stated
Agar
Sucrose
Methyl-p-hydroxybenzoate (E218)
Propyl-p-hydroxybenzoate (E216)
Potassium sorbate
Sodium metabisulphite (E223)
Tween 80
Raspberry essence (Contains small amount of ethanol)
Saccharin
Diethanolamine
Purified water
The following CIOMS frequency rating is used, when applicable:
Very common > 10 %; Common > 1 and <10%; Uncommon > 0.1 and <1%; Rare > 0.01 and <0.1%; Very rare <0.01%, Unknown (cannot be estimated from available data).
Reactions occurring with either daily or intermittent dosage regimens include:
Infections and infestations
Unknown: Pseudomembranous colitis, influenza
Blood and lymphatic system disorders
Common: Thrombocytopenia with or without purpura, usually associated with intermittent therapy, but is reversible if drug is discontinued as soon as purpura occurs.
Uncommon: leukopenia
Unknown: Disseminated intravascular coagulation,eosinophilia, agranulocytosis, hemolytic anemia
Immune system disorders
Unknown: anaphylactic reaction
Endocrine disorders
Unknown: adrenal insufficiency in patients with compromised adrenal function have been observed.
Metabolism and nutritional disorders
Unknown: decreased appetite
Psychiatric disorders
Unknown: Psychotic disorder
Nervous system disorders
Common: headache, dizziness
Unknown: Cerebral hemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura.
Eye disorders
Unknown: Tear discoloration
Vascular disorders
Unknown: Shock, flushing, vasculitis
Respiratory, thoracic and mediastinal disorders
Unknown: Dyspnoea, wheezing, sputum discoloured
Gastrointestinal disorders
Common: Nausea, vomiting
Uncommon: Diarrhea
Unknown: Gastrointestinal disorder, abdominal discomfort, tooth discoloration (which may be permanent)
Hepatobiliary disorders
: Special warnings and precautions for use)Skin and subcutaneous tissue disorders
Unknown: Erythema multiforme including Stevens-Johnson syndrome and toxic epidermal necrolysis, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome , skin reaction, pruritus, rash pruritic, urticaria, dermatitis allergic, pemphigoid, sweat discoloration.
Musculoskeletal and connective tissue disorders
Unknown: Muscle weakness, myopathy, bone pain
Renal and urinary disorders
Unknown: acute kidney injury usually due to renal tubular necrosis or tubulointerstitial nephritis, chromaturia
Pregnancy, puerperium and perinatal conditions
Unknown: Post-partum haemorrhage, fetal-maternal haemorrhage
Reproductive system and breast disorders
Unknown: Menstrual disorder
Congenital, familial and genetic disorders
Unknown: Porphyria
General disorders and administration site conditions
Very common: Pyrexia, chills
Unknown: Edema
Investigations
Common: Blood bilirubin increased, aspartate aminotransferase increased, alanine aminotransferase increased
Unknown: Blood pressure decreased, blood creatinine increased, hepatic enzyme increased
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Not applicable
Rifampicin is an active bactericidial antituberculosis drug which is particularly active against the rapidly growing extracellular organisms and also has bactericidial activity intracellularly. Rifampicin has activity against slow and intermittently-growing M. Tuberculosis.
Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown with other rifamycins.
Rifampicin is readily absorbed from the gastrointestinal tract. Peak serum concentrations of the order of 10 µg/ml occur about 2 to 4 hours after a dose of 10 mg/kg body weight on an empty stomach.
Absorption of rifampicin is reduced when the drug is ingested with food.
The pharmacokinetics (oral and intravenous) in children are similar to adults.
In normal subjects the biological half-life of rifampicin in serum averages about 3 hours after a 600 mg dose and increases to 5.1 hours after a 900 mg dose. With repeated administration, the half-life decreases and reaches average values of approximately 2-3 hours. At a dose of up to 600 mg/day, it does not differ in patients with renal failure and consequently, no dosage adjustment is required.
Rifampicin is rapidly eliminated in the bile and an enterophepatic circulation ensues. During this process, rifampicin undergoes progressive deacetylation, so that nearly all the drug in the bile is in this form in about 6 hours. This metabolite retains essentially complete antibacterial activity. Intestinal reabsorption is reduced by deacetylation and elimination is facilitated. Up to 30 % of a dose is excreted in the urine, with about half of this being unchanged drug.
Rifampicin is widely distributed throughout the body. It is present in effective concentrations in many organs and body fluids, including cerebrospinal fluid. Rifampicin is about 80 % protein bound. Most of the unbound fraction is not ionized and therefore is diffused freely in tissues.
19/02/2018
Aventis Pharma Limited
Trading as Marion Merrell or Aventis Pharma
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
Or trading as
Sanofi-aventis or Sanofi
One Onslow Street
Guildford
Surrey
GU1 4YS
UK
Do not store above 25°C.
Do not dilute.
Dispense in clear or amber glass bottles.
120ml in amber glass bottles
PL 04425/5917R
Rifampicin should be given under the supervision of a respiratory or other suitably qualified physician.
Cautions should be taken in case of renal impairment if dose > 600 mg/day.
All tuberculosis patients should have pre-treatment measurements of liver function.
Adults treated for tuberculosis with rifampicin should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count, and a platelet count (or estimate).
Baseline tests are unnecessary in children unless a complicating condition is known or clinically suspected.
Patients with impaired liver function should only be given rifampicin in cases of necessity, and then with caution and under close medical supervision. In these patients, lower doses of rifampicin are recommended and careful monitoring of liver function, especially serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) should initially be carried out prior to therapy, weekly for two weeks, then every two weeks for the next six weeks. If signs of hepatocellular damage occur, rifampicin should be withdrawn.
Rifampicin should also be withdrawn if clinically significant changes in hepatic function occur. The need for other forms of antituberculosis therapy and a different regimen should be considered. Urgent advice should be obtained from a specialist in the management of tuberculosis. If rifampicin is re-introduced after liver function has returned to normal, liver function should be monitored daily.
In patients with impaired liver function, elderly patients, malnourished patients, and possibly, children under two years of age, caution is particularly recommended when instituting therapeutic regimens in which isoniazid is to be used concurrently with Rifadin. If the patient has no evidence of pre-existing liver disease and normal pre-treatment liver function, liver function tests need only be repeated if fever, vomiting, jaundice or other deterioration in the patient's condition occur.
Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions.
In some patients hyperbilirubinaemia can occur in the early days of treatment. This results from competition between rifampicin and bilirubin for hepatic excretion.
An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather the decision should be made after repeating the tests, noting trends in the levels and considering them in conjunction with the patient's clinical condition.
Because of the possibility of immunological reaction including anaphylaxis occurring with intermittent therapy (less than 2 to 3 times per week) patients should be closely monitored. Patients should be cautioned against interrupting treatment.
Rifampicin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D. Isolated reports have associated porphyria exacerbation with rifampicin administration.
Severe, systemic hypersensitivity reactions, including fatal cases, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome have been observed during treatment with anti-tuberculosis therapy.
It is important to note that early manifestations of hypersensitivity, such as fever, lymphadenopathy or biological abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be advised to consult immediately their physician.
Rifadin Oral Suspension should be discontinued if an alternative etiology for the signs and symptoms cannot be established.
Rifadin Oral Suspension contains sodium metabisulfite which may cause allergic type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
The suspension contains 2 g of sucrose per 5 ml dose. This should be taken into account in patients with diabetes mellitus. This may also be harmful to teeth. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.
Rifadin Oral Suspension contains 7.2mg of sodium (0.24mg/ml) per 600 mg daily dose and is essentially 'sodium-free'.
Rifadin Oral Suspension contains Methyl-p-hydroxybenozoate and propyl-p-hydroxybenzoate, these may cause allergic reactions (possibly delayed).
This medicine contains potassium, less than 1 mmol (10.4mg) per 30ml dose, i.e. is essentially 'potassium free'.
Rifadin Oral Suspension may produce discoloration (yellow, orange, red, brown) of the teeth, urine, sweat, sputum and tears, and the patient should be forewarned of this. Soft contact lenses have been permanently stained.
All patients with abnormalities should have follow up examinations, including laboratory testing, if necessary.
None stated
Not applicable
23/03/05
