Rifampin

Rifampicin is an antibiotic belonging to the class of rifamycins. It is a semi-synthetic compound that derives from rifamycin B, produced by Nocardia mediterranei .

Rifampicin - Chemical Structure

Rifampicin has a bactericidal action (i.e. is able to kill bacteria) and is marketed in the form of pharmaceutical formulations suitable for both oral and parenteral administration.

Indications

For what it uses

Rifampicin monotherapy is used for the prophylaxis of infections caused by Neisseria meningitidis and Haemophilus influenzae .

Instead, in association with other antibiotics, rifampicin is used in the treatment of:

Tuberculosis;
Leprosy;
endocarditis;
osteomyelitis;
Severe Legionellosis;
Acute Brucellosis;
Complicated urinary tract infections.

Warnings

Adult patients, before starting treatment with rifampicin, must undergo blood cell counting and controls to determine blood levels of bilirubin, liver enzymes and creatinine.

Rifampicin has an enzyme-inducing capacity and, therefore, can cause an increase in the metabolism of many endogenous substrates, including vitamin D and hormones produced by the thyroid and adrenal glands.

Rifampicin may cause a worsening of porphyria in patients who are affected.

Rifampicin can give red color to urine, sweat, tears and sputum. Furthermore, soft contact lenses worn by patients on rifampicin therapy have been reported to have a permanent red color.

A great deal of caution should be used when administering rifampicin in early infancy and in elderly patients with a poor nutritional status, especially when the antibiotic is used in combination with isoniazid for the treatment of tuberculosis.

The administration of rifampicin in patients with impaired renal function should only be performed if really necessary and under strict medical supervision. The liver function of these patients must be constantly monitored. If symptoms of possible liver toxicity appear, treatment with rifampicin should be discontinued.

Rifampicin may decrease the effectiveness of oral contraceptives, therefore, it is advisable to use non-hormonal methods of contraception for the duration of the antibiotic therapy.

Interactions

Rifampicin is an inducer of hepatic cytochrome P450 enzymes, therefore, it can promote the elimination and, consequently, reduce the efficacy of drugs metabolised by the same cytochrome P450. Among these drugs, we recall:

Anticonvulsants ;
Antiarrhythmics ;
Some anticancer drugs;
Antipsychotics ;
Tricyclic antidepressants ;
Oral anticoagulants ;
Barbiturates and benzodiazepines ;
Chloramphenicol (an antibiotic);
Fluoroquinolones (antibacterial drugs);
Oral contraceptives ;
Corticosteroids ;
Opioid analgesics ;
Antiemetics (antivomit);
Levothyroxine ;
Theophylline .

Concomitant administration of rifampicin and saquinavir and ritonavir (antiviral drugs used in the treatment of AIDS) may increase the risk of liver toxicity. Therefore, this association must be avoided.

The risk of hepatotoxicity also increases with concomitant administration of rifampicin and halothane (a general anesthetic) or isoniazid (used to treat malaria). Therefore, the concomitant use of rifampicin and halothane should be avoided, while patients on rifampicin and isoniazid therapy should be carefully monitored.

The concomitant administration of atovaquone (a drug used in the treatment of malaria) and rifampicin causes a decrease in the plasma concentration of atovaquone and an increase in the rifampicin plasma concentration.

Concomitant use of ketoconazole (an antifungal) and rifampicin causes a decrease in the blood concentration of both drugs.

Rifampicin causes an increase in the plasma concentration of the active metabolite of enalapril (an ACE inhibitor) when administered together. Therefore, the dose of enalapril administered may need to be adjusted.

Antacid drugs can reduce the absorption of rifampicin.

In any case, it is always good to inform your doctor if you are taking - or if you have recently been - medicines of any kind, including non-prescription medicines and herbal and / or homeopathic products.

Side effects

Rifampicin can cause various side effects, although not all patients experience them. This is because each person has their own sensitivity to the drug. Therefore, it is said that the undesirable effects do not all occur with the same intensity in each patient.

The main side effects that may occur during rifampicin therapy are listed below.

Hepatobiliary disorders

Treatment with rifampicin may induce hepatotoxicity and lead to the onset of hepatitis.

Gastrointestinal disorders

Rifampicin therapy can cause:

Nausea and vomit;
Diarrhea;
Abdominal discomfort;
Pseudomembranous colitis.

Skin and subcutaneous tissue disorders

During treatment with rifampicin skin reactions such as redness, itching and a minor rash may occur.

More rarely, more severe reactions may occur, such as pemphigoid reaction, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Blood and lymphatic system disorders

During rifampicin therapy, cases of:

Plateletopenia (ie the decrease in the number of platelets in the bloodstream) accompanied by purple or not;
Leukopenia, ie the decrease in blood levels of leukocytes;
Eosinophilia, that is the increase in the number of eosinophils in the bloodstream;
Acute hemolytic anemia.

Furthermore - although rare - cases of agranulocytosis have been reported, that is a severe decrease in the number of granulocytes in the bloodstream.

Kidney and urinary tract disorders

Treatment with rifampicin may cause adrenal insufficiency in patients with previous impairment of adrenal function and acute renal failure caused by acute interstitial nephritis or acute tubular necrosis.

Other side effects

Other side effects that may occur during treatment with rifampicin are:

Edema;
Muscle weakness;
myopathy;
Temperature;
Chills;
Headache;
dizziness;
Bone pain;
Dyspnoea;
Wheezing;
Lowering of blood pressure and shock;
Anaphylaxis.

Overdose

The symptoms that can occur if overdose of rifampicin is taken are:

Nausea and vomiting, even severe;
Abdominal pain;
Headache;
Itch;
Lethargy;
Transient increases in blood levels of bilirubin and liver enzymes;
Brown-reddish coloring of the skin, urine, faeces, sweat and tears, whose intensity varies according to the amount of drug taken;
Facial and periorbital edema;
Hypotension;
Ventricular arrhythmias;
Sinus tachycardia;
Cardiac arrest;
Convulsions;
Loss of consciousness.

Treatment for rifampicin overdose should be supportive and symptoms should be treated as they arise.

Gastric lavage and administration of activated charcoal may be useful to eliminate excess antibiotic from the gastrointestinal tract.

In some patients, hemodialysis may also be useful.

Action mechanism

Rifampicin exerts its antibacterial action by preventing DNA transcription. More precisely, rifampicin inhibits bacterial dependent RNA-polymerase DNA. This enzyme is able to transcribe the genetic information contained in DNA into a complementary RNA molecule.

By preventing the bacterial cell from accessing its genetic information, the various cellular activities stop and eventually lead to the death of the cell itself.

Mode of Use - Posology

Rifampicin is available for intravenous administration as a powder and solvent for infusion and for oral administration in the form of capsules, tablets and syrup.

During therapy with rifampicin it is necessary to follow the instructions given by the doctor, both as regards the amount of drug to be taken and the duration of the treatment.

Oral administration

To promote the absorption of rifampicin, it is advisable to take the drug on an empty stomach and away from meals.

For the treatment of tuberculosis in adult patients with body weight over 50 kg, the usual administered rifampicin dose is 600 mg per day. For patients with a body weight of less than 50 kg, the dose of medication usually used is 450 mg per day.

During the treatment of tuberculosis, rifampicin is always given in combination with other antibiotics.

For the treatment of other infections, the usual dose of rifampicin is 900-1200 mg a day, to be taken in two divided doses.

In children, the recommended rifampicin dose is 10-20 mg / kg of body weight, to be taken in two divided doses. Children should not be given a daily dose of more than 600 mg of the drug.

Intravenous administration

The administration of intravenous rifampicin is indicated when the patient's condition does not allow oral administration.

For both the treatment of tuberculosis and the treatment of other types of infections, the dose of rifampicin usually given to adults by intravenous infusion is 600 mg of the drug.

Pregnancy and breastfeeding

Rifampicin is able to cross the placenta, but the effects it may have on the fetus are not known. Studies conducted on rodents, however, have shown that high-dose rifampicin can cause teratogenic effects. Furthermore, if administered during the last weeks of pregnancy, rifampicin may promote the emergence of post-natal haemorrhages in the newborn and in the mother that require adequate treatment with vitamin K.

In light of these facts, rifampicin should be used by pregnant women only if the expected potential benefits to the mother outweigh the potential risks to the fetus and only under strict medical supervision. The same goes for the use of the antibiotic by mothers who are breast-feeding.