Aptecin

Uses

In the treatment of both tuberculosis and the meningococcal carrier state, the small number of resistant cells present within large populations of susceptible cells can rapidly become the predominant type. Bacteriologic cultures should be obtained before the start of therapy to confirm the susceptibility of the organism to rifampinand they should be repeated throughout therapy to monitor the response to treatment. Since resistance can emerge rapidly, susceptibility tests should be performed in the event of persistent positive cultures during the course of treatment. If test results show resistance to rifampin and the patient is not responding to therapy, the drug regimen should be modified.

Aptecin is also used to associated treatment for these conditions: Cholestatic pruritus, MRSA Infection, Prosthetic Joint Infection, Asymptomatic Neisseria meningitidis carrier of the nasopharynx, Initial phase Tuberculosis, Late phase Tuberculosis, Antibacterial therapy

How Aptecin works

Rifampin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Dosage

Aptecin dosage

Rifampin can be administered by the oral route or by IV infusion. IV doses are the same as those for oral.

Tuberculosis:

• Adults: 10 mg/kg, in a single daily administration, not to exceed 600 mg/day, oral or IV
• Pediatric Patients: 10–20 mg/kg, not to exceed 600 mg/day, oral or IV

It is recommended that oral rifampin be administered once daily, either 1 hour before or 2 hours after a meal with a full glass of water.

Rifampin is indicated in the treatment of all forms of tuberculosis. A three-drug regimen consisting of rifampin, isoniazid, and pyrazinamide is recommended in the initial phase of shortcourse therapy which is usually continued for 2 months. The Advisory Council for the Elimination of Tuberculosis, the American Thoracic Society, and theCenters for Disease Control and Preventionrecommend that either streptomycin or ethambutol be added as a fourth drug in a regimen containing isoniazid (INH), rifampin and pyrazinamide for initial treatment of tuberculosis unless the likelihood of INH resistance is very low. The need for a fourth drug should be reassessed when the results of susceptibility testing are known. If community rates of INH resistance are currently less than 4%, an initial treatment regimen with less than four drugs may be considered.

Following the initial phase, treatment should be continued with rifampin and isoniazid for at least 4 months. Treatment should be continued for longer if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive.

Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals.

Preparation Of Solution For IV Infusion: Reconstitute the lyophilized powder by transferring 10 mL of sterile water for injection to a vial containing 600 mg of rifampin for injection. Swirl vial gently to completely dissolve the antibiotic. The reconstituted solution contains 60 mg rifampin per mL and is stable at room temperature for up to 30 hours. Prior to administration, withdraw from the reconstituted solution a volume equivalent to the amount of rifampin calculated to be administered and add to 500 mL of infusion medium. Mix well and infuse at a rate allowing for complete infusion within 3 hours. Alternatively, the amount of rifampin calculated to be administered may be added to 100 mL of infusion medium and infused in 30 minutes.

Dilutions in dextrose 5% for injection (D5W) are stable at room temperature for up to 8 hours and should be prepared and used within this time. Precipitation of rifampin from the infusion solution may occur beyond this time. Dilutions in normal saline are stable at room temperature for up to 6 hours and should be prepared and used within this time. Other infusion solutions are not recommended.

Side Effects

Facial flushing and itching, with or without a rash, flu-like syndrome characterised by episodes of fever, chills, headache, dizziness, bone pain, shortness of breath, and malaise; GI adverse effects (e.g. nausea, vomiting, anorexia, diarrhoea, epigastric distress), pseudomembranous colitis, eosinophilia, leucopenia, haemolytic anaemia; alterations in kidney function and renal failure, menstrual disturbances, oedema, myopathy, muscular weakness; orange-red discolouration of the urine, faeces, sweat, saliva, sputum, tears, and other body fluids; thrombophlebitis, local irritation and inflammation after prolonged IV infusion. Rarely, eye irritation and visual disturbances, anaphylaxis or shock.

Toxicity

LD₅₀=1570 mg/kg (rat), chronic exposure may cause nausea and vomiting and unconsciousness

Precaution

Aptecin has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Patients with impaired liver function should be given rifampin only in cases of necessity and then with caution and under strict medical supervision. In these patients, careful monitoring of liver function, especially SGPT/ALT and SGOT/AST should be carried out prior to therapy and then every 2 to 4 weeks during therapy. If signs of hepatocellular damage occur, rifampin should be withdrawn.

In some cases, hyperbilirubinemia resulting from competition between rifampin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. 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.

Rifampin has enzyme-inducing properties, including induction of delta amino levulinic acid synthetase. Isolated reports have associated porphyria exacerbation with rifampin administration.

Interaction

May accelerate the metabolism and reduce the effect of drugs that are metabolised by CYP450 enzymes (e.g. quinidine, phenytoin, theophylline). Decreased concentrations of atovaquone and increased concentrations of rifampicin when taken concomitantly. Concurrent use of ketoconazole and rifampicin may result in decreased serum concentrations of both drugs. May decrease serum concentrations of enalaprilat. Reduced absorption by antacids. Increased risk of hepatotoxicity with halothane or isoniazid.

Food Interaction

• Avoid alcohol.
• Take on an empty stomach. Take at least 1 hour before or 2 hours after meals.
• Take with a full glass of water.

Elimination Route

Well absorbed from gastrointestinal tract.

Half Life

3.35 (+/- 0.66) hours

Clearance

• 0.19 +/- 0.06 L/hr/kg [300 mg IV]
• 0.14 +/- 0.03 L/hr/kg [600 mg IV]

Elimination Route

Less than 30% of the dose is excreted in the urine as rifampin or metabolites.

Pregnancy & Breastfeeding use

Pregnancy: When administered during the last few weeks of pregnancy, rifampin can cause post natal hemorrhages in the mother and infant for which treatment with vitamin K may be indicated.

Nursing Mothers: Because of the potential for tumorigenicity shown for rifampin in animal studies, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Aptecin is contraindicated in patients with a history of hypersensitivity to rifampin or any of the components, or to any of the rifamycins. Rifampin is contraindicated in patients who are also receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity.

Rifampin is contraindicated in patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance.

Special Warning

Geriatric Use: Clinical studies of Aptecin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Caution should therefore be observed in using rifampin in elderly patients.

Acute Overdose

Nausea, vomiting, abdominal pain, pruritus, headache, and increasing lethargy will probably occur within a short time after ingestion; unconsciousness may occur when there is severe hepatic disease. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces will occur, and its intensity is proportional to the amount ingested.

Liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage; bilirubin levels may increase and jaundice may develop rapidly. Hepatic involvement may be more marked in patients with prior impairment of hepatic function. Other physical findings remain essentially normal. A direct effect upon the hematopoietic system, electrolyte levels, or acid-base balance is unlikely.

Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.

Storage Condition

Store between 15-30° C. Avoid excessive heat and protect from light.

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