Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Drug class: Rifamycin antibacterial
Main indication: Resistant staphylococcal and mycobacterial infections
Available forms4 forms · 5 strengths documentedShow all ↓
Oral · solid
Capsule 150 mg Rifadin® · Rimactane® · genericCapsule 300 mgCombination capsule rifampicin 35 mg + azithromycin 30 mg veterinary special
Oral · liquid
Syrup 20 mg/mL
Injection
Lyophilized powder 600 mg/vial Rifadin® IV; intravenous infusion only
Availability
No veterinary-labelled product is available
Overview
Rifampin (Rifampicin) is a broad-spectrum antimicrobial used in dogs and cats. It has activity against a variety of organisms including Gram-positive bacteria, Chlamydia, Rickettsia, certain protozoa and Mycobacteria, while Gram-negative aerobic bacteria are usually innately resistant.
In small animal medicine, rifampin has been used as part of combination antimicrobial protocols for selected mycobacterial infections and resistant staphylococcal infections. Because resistance develops readily, it is generally administered in combination with other antimicrobial agents.
Mechanism of Action (MOA): Rifampin binds to the beta subunit of bacterial, but not mammalian, DNA-dependent RNA polymerase, resulting in abortive initiation of RNA synthesis.
Indications
Rifampin is used in dogs and cats for selected bacterial and mycobacterial infections, typically as part of combination antimicrobial therapy.
- Mycobacterial infections: Used as part of combination treatment protocols for tuberculous and non-tuberculous mycobacterial infections.
- Rhodococcus equi-associated lesions (cats): May be used in cats with lesions associated with Rhodococcus equi.
- Staphylococcal pyoderma: May be useful in the treatment of staphylococcal pyoderma that is resistant to first-line therapies, including methicillin-resistant Staphylococcus pseudintermedius pyoderma in dogs; it is a third-line choice, used only where culture confirms susceptibility and topical antiseptics are not feasible or effective.
- Ehrlichiosis and bartonellosis : May be considered as part of the management of these infections. Canine ehrlichiosis has a published rifampin regimen and is set out in the dog dose table; in canine bartonellosis rifampin is one of several options that must be combined with another agent — single-agent antibiotic therapy is not efficacious.
- Canine leproid granuloma: In dogs, rifampin may help nodular leproid granuloma lesions resolve when it is combined with a second antimicrobial; the regimen and its companion agents are set out in the dog dose table.
- Canine brucellosis: Rifampin may be used in dogs as part of a combination regimen when treatment of Brucella canis is attempted, although antibiotic therapy is not encouraged except in select cases, due to the zoonotic risk and because there is no known cure.
- Feline mycobacterial disease: Feline leprosy syndromes and other mycobacterial infections in cats are treated with rifampin as one component of a two- or three-drug protocol; the regimens, their companion agents and their durations are set out in the cat dose table.
- Nontuberculous mycobacterial infection: Rifampin is also combined with other antimycobacterial drugs for nontuberculous mycobacterial infection, and with amphotericin B and flucytosine for histoplasmosis or aspergillosis involving the central nervous system.
Dosage (Reference)
Dog
Rifampin is used in selected bacterial skin infections, particularly when first-line antimicrobial therapy is inappropriate or when culture and susceptibility testing support its use.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Superficial bacterial folliculitis | PO | 5 mg/kg | q12h | 5 mg/kg PO q12h (preferred); alternatively, 10 mg/kg PO q24h. Do not exceed a total daily dose of 10 mg/kg. Reserve rifampin as a third-line option when cephalexin, amoxicillin–clavulanate, or clindamycin and topical therapy are unsuitable and culture confirms susceptibility. Treat until lesions resolve and cytology is normal, generally 7 days beyond surface healing (commonly 3–4 weeks). |
| Methicillin-resistant Staphylococcus spp. pyoderma | PO | 5 mg/kg | q12h | Administer with topical antimicrobials for 4–5 weeks, and consult a specialist before starting treatment. |
| Canine leproid granuloma | PO | 10–15 mg/kg (maximum 600 mg total) | q24h | Excision is curative and the lesions may self-cure; antimicrobial therapy may assist healing. Where drug therapy is used, combine rifampin with an agent effective against slow-growing nontuberculous mycobacteria such as clofazimine, clarithromycin or pradofloxacin. For severe or refractory disease, rifampin 10–15 mg/kg PO once daily may be combined with clarithromycin 7.5–12.5 mg/kg PO two to three times daily and topical silver sulfasalazine. |
| Canine ehrlichiosis (Ehrlichia canis) | PO | 10 mg/kg | q24h | Alternative to a tetracycline and considered less effective. Give for 3 weeks and do not exceed 10 mg/kg per day in dogs. |
| Canine brucellosis (Brucella canis) | PO | 5 mg/kg | q24h | Only where treatment is attempted despite the zoonotic risk and the absence of a known cure; if it is attempted, isolate the infected dog from other dogs and breeding animals. Published protocols differ: one combines rifampin 5 mg/kg PO q24h with doxycycline 10 mg/kg PO q12h and gentamicin 5 mg/kg SC q24h for 3 months; another reports 7-day gentamicin courses repeated every 3 weeks with antimicrobial treatment for 1 to 3 months. Retest after treatment and repeat therapy until testing is negative; after negative serology, retest every 4 to 6 months and repeat treatment as necessary. |
Important dosing notes (dogs):
• Combination with another effective antimicrobial is generally recommended to reduce the emergence of resistance, although resistance may still develop rapidly during combination therapy. For staphylococcal infections, guidance differs: rifampin monotherapy has been considered acceptable because clinical evidence demonstrating that an additional antimicrobial is necessary is lacking.
• Dogs—superficial bacterial folliculitis: 5 mg/kg PO q12h is preferred, with a maximum total daily dose of 10 mg/kg. Monitor liver enzymes and bilirubin as outlined under Warnings, particularly during prolonged treatment or if higher doses are used.
• Combination with another effective antimicrobial is generally recommended to reduce the emergence of resistance, although resistance may still develop rapidly during combination therapy. For staphylococcal infections, guidance differs: rifampin monotherapy has been considered acceptable because clinical evidence demonstrating that an additional antimicrobial is necessary is lacking.
• Dogs—superficial bacterial folliculitis: 5 mg/kg PO q12h is preferred, with a maximum total daily dose of 10 mg/kg. Monitor liver enzymes and bilirubin as outlined under Warnings, particularly during prolonged treatment or if higher doses are used.
Cat
Rifampin has been used as part of combination antimicrobial therapy for feline leprosy syndromes.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Feline leprosy syndromes | PO | 10–15 mg/kg | q24h | Combine with clofazimine, clarithromycin, or pradofloxacin; continue until lesion resolution and ideally for a further 2–3 months. Some cases may require lifelong clarithromycin. |
| Mycobacterial infection (tuberculous and non-tuberculous) | PO | 10–15 mg/kg | q24h | Protocols differ. Pending diagnosis, use pradofloxacin alone for localized disease or with azithromycin for extensive disease; add rifampin if tuberculosis is confirmed. Use triple therapy for 4–6 months and ≥2 months beyond lesion resolution; NTM infections require ≥2 susceptibility-guided agents for 6–9 months, although indefinite treatment may be necessary. |
Important dosing notes (cats):
• Use rifampin only as part of combination antimicrobial therapy. Rifampin, pradofloxacin, and azithromycin are commonly used initially, while clofazimine or clarithromycin may be included according to the mycobacterial species and clinical response. A feeding tube may be required for reliable long-term administration.
• For treatment-associated pruritus, edema, or erythema, chlorphenamine may be given at 2–4 mg/cat PO q8–12h; focal lesions may also be treated with topical hydrocortisone aceponate.
• If hepatotoxicity develops, S-adenosylmethionine may be given at 20 mg/kg PO q24h. N-acetylcysteine, 600 mg/cat PO q12h, is an alternative, although feline pharmacological data are limited. Use cautiously in asthmatic cats and administer as intact capsules when possible to minimize its unpleasant taste and associated nausea, vomiting, or drooling.
• Use rifampin only as part of combination antimicrobial therapy. Rifampin, pradofloxacin, and azithromycin are commonly used initially, while clofazimine or clarithromycin may be included according to the mycobacterial species and clinical response. A feeding tube may be required for reliable long-term administration.
• For treatment-associated pruritus, edema, or erythema, chlorphenamine may be given at 2–4 mg/cat PO q8–12h; focal lesions may also be treated with topical hydrocortisone aceponate.
• If hepatotoxicity develops, S-adenosylmethionine may be given at 20 mg/kg PO q24h. N-acetylcysteine, 600 mg/cat PO q12h, is an alternative, although feline pharmacological data are limited. Use cautiously in asthmatic cats and administer as intact capsules when possible to minimize its unpleasant taste and associated nausea, vomiting, or drooling.
Warnings & Precautions
Rifampin should be used carefully due to its potential for hepatotoxicity – which can be fatal in some dogs – and the rapid development of antimicrobial resistance when it is used as a single agent.
- Combination therapy: Rifampin should be used in combination with other antimicrobial agents to reduce the emergence of resistant organisms.
- Hepatic disease: Rifampin should not be administered to animals with liver disease and should be used with caution in patients with pre-existing hepatic dysfunction. Dogs may be more susceptible to hepatotoxicity than other species.
- Pregnancy: Rifampin may be teratogenic at high doses; avoid use during pregnancy unless the expected maternal benefit clearly outweighs the potential risk to the offspring.
- Lactation: Rifampin is excreted in maternal milk; use it with caution in nursing animals.
- Monitoring of liver function: Obtain baseline liver enzymes and bilirubin, repeat after 7–14 days, and monitor every 2 weeks thereafter; stable animals receiving prolonged therapy should be assessed at least monthly. In cats, perform haematology and serum biochemistry 2 weeks after treatment begins and whenever demeanour changes. During antituberculosis or antileprosy therapy, examine the patient monthly, including appetite, body weight, liver profile, and skin. Advise owners to report cutaneous lesions immediately. Monitor older animals particularly closely, and discontinue rifampin if liver enzyme activities increase.
- Handling precautions: People who are or may become pregnant should not handle this drug.
- Hypersensitivity: Do not use in animals with known hypersensitivity to rifampin or to any other rifamycin.
- Hepatopathy in cats: In cats treated for mycobacterial infection, signs of liver dysfunction including inappetence, vomiting or jaundice may occur, and the hepatopathy can be fatal.
- Zoonotic and public-health considerations: Feline mycobacterial disease may be caused by a member of the tuberculosis complex and carries a zoonotic risk: do not attempt treatment without agreement from the public health authorities, and do not treat where immunosuppressed household members may be exposed, or where the cat has generalized disease, cavitating respiratory lesions or extensive draining cutaneous lesions.
- Pancreatitis: Use with caution in animals at risk of pancreatitis.
- Antimicrobial stewardship: Rifampin is classified as category A (Avoid) by the European Medicines Agency and is designated a Critically Important (High Priority) Antimicrobial for human medicine, so it should be reserved for cases where culture confirms susceptibility and no lower-tier option exists.
- Injectable route: There is no veterinary-licensed product. If the human injectable form is used, administer it only by intravenous infusion over at least 30 minutes; extravasation must be avoided, and it must never be given by the intramuscular or subcutaneous route.
- Infusion diluent and stability: Use 5% dextrose as the infusion diluent unless the product instructions specifically permit 0.9% sodium chloride. The reconstituted vial is stable for 24 hours, whereas the diluted infusion should be administered within 4 hours of preparation. Confirm compatibility with all IV fluids and injectable drugs before mixing; administer separately if compatibility is uncertain.
Drug Interactions
Rifampin is one of the most potent inducers of hepatic cytochrome P450 enzymes and is also an inducer of the P-glycoprotein efflux pump, so it may increase the metabolism and reduce the absorption of concurrently administered drugs. Unless stated otherwise, these interactions do not necessarily contraindicate concurrent use; weigh the risks and perform additional monitoring when appropriate.
- Barbiturates: Rifampin may increase the rate of metabolism of barbiturates, potentially reducing their clinical effect.
- Theophylline: Rifampin may increase the rate of metabolism of theophylline, potentially reducing therapeutic concentrations.
- Itraconazole: Rifampin may increase the rate of metabolism of itraconazole, potentially reducing its effectiveness.
- Fluoroquinolones: Rifampin may reduce fluoroquinolone concentrations and in vitro antagonism has been reported, so one reference advises avoiding the combination; other references nevertheless include enrofloxacin among the agents combined with rifampin for mycobacterial and brucellar disease.
- Clarithromycin: Rifampin may reduce clarithromycin concentrations; clarithromycin nevertheless remains a named companion agent in feline mycobacterial protocols.
- Interactions with other consequences: Some interactions do not simply lower a drug level: rifampin may decrease serum atovaquone concentrations; increase the risk of bleeding with clopidogrel by increasing formation of its active metabolite; increase concentrations of active cyclophosphamide metabolites; increase the risk of nephrotoxicity and neurotoxicity with ifosfamide; increase the risk of hepatotoxicity with leflunomide and with isoniazid; enhance the hypotensive effect of propofol; and, in combination with doxycycline, cause hemolytic anemia and elevated liver enzymes.
- Drugs whose concentrations may fall: Rifampin induces hepatic microsomal enzymes, so drugs metabolized by those enzymes may have their elimination half-lives shortened and their serum levels decreased. Concentrations of many other drugs may fall, including amiodarone, azole antifungals, benzodiazepines, beta blockers, buspirone, calcitriol, cannabidiol, chloramphenicol, corticosteroids, cyclosporine, dapsone, digoxin, diltiazem, doxorubicin, doxycycline, enalapril, estrogens, glipizide, ketamine, lidocaine and mexiletine, mycophenolate, ondansetron, opioids, phenobarbital, progestins, proton pump inhibitors, quinidine, rivaroxaban, sertraline, potentiated sulfonamides, theophylline, vincristine and warfarin. An interaction with levothyroxine is also reported.
- Praziquantel: Avoid concurrent praziquantel — the combination is contraindicated in humans since therapeutically effective blood levels of praziquantel may not be achieved.
- Other hepatotoxic drugs: Combining rifampin with another potentially hepatotoxic drug — a sulfonamide, an anticonvulsant or acetaminophen — increases the risk of liver injury, and rifampin may increase acetaminophen toxicity in its own right.
- Terbinafine: Rifampin decreases terbinafine blood concentrations.
Side Effects & Overdose
Side Effects
Adverse effects associated with rifampin are primarily related to hepatic effects, gastrointestinal upset and discoloration of body fluids.
- Increased hepatic enzymes: Elevations in serum hepatic enzyme concentrations are commonly reported in dogs — alkaline phosphatase rises are common, and reported series put raised ALT at about a quarter of treated dogs and reversible enzyme elevations at 27%.
- Clinical hepatitis: Hepatic enzyme elevations may progress to clinical hepatitis, and some dogs develop a fatal hepatotoxicity.
- Orange-red discoloration: Rifampin metabolites may cause orange-red discoloration of urine, feces, saliva, tears, sweat, sclera and mucous membranes; the discoloration is harmless and normal, but it can stain fabrics.
- Gastrointestinal effects: Gastrointestinal disturbances — vomiting, diarrhea and anorexia — are commonly reported; in one canine series 16% of dogs given 2.9 to 16 mg/kg per day showed adverse effects, including vomiting in 7%, anorexia in 6% and lethargy in 4%.
- Haematological and renal effects: Thrombocytopenia, hemolytic anemia and acute kidney injury are rarely reported, and a partial, reversible immunosuppression of lymphocytes develops during treatment.
- Palatability: Rifampin is unpalatable and bitter, so it may be difficult to administer and can cause a decreased appetite during treatment.
- Pancreatic effects: Pancreatitis has been associated with rifampin administration, although it is not well documented in dogs or cats.
- Rashes and intermittent-dosing reactions: Hypersensitivity reactions can occur, and renal failure is a possible consequence when intermittent dosing schedules are used. Rashes are an uncommon adverse effect.
Overdose
- Clinical signs of oral rifampin overdose are generally extensions of the usual adverse effects, with gastrointestinal upset and red-orange coloring of fluids and skin, but massive overdoses may cause hepatotoxicity.
- Should a massive oral overdose occur, standard GI decontamination protocols should be followed. Liver enzymes should be monitored, and supportive treatment should be initiated if necessary.
- For a known or suspected overdose, consultation with a 24-hour poison control center able to provide veterinary-specific information is recommended.
Key Notes
Practical clinical points for the use of rifampin in dogs and cats:
- Resistance development: Chromosomal mutations may rapidly result in antimicrobial resistance — a single mutation in the beta subunit of DNA-dependent RNA polymerase is enough, producing a one-step resistance process.
- Activity against resistant infections: May provide a therapeutic option in selected staphylococcal infections that have failed first-line treatments.
- Role in mycobacterial disease: Often incorporated into multidrug treatment protocols for mycobacterial infections. In cats the published protocols differ: one is built on rifampin with pradofloxacin and azithromycin, another on a fluoroquinolone with clarithromycin and doxycycline, and where triple therapy is not feasible two drugs are used instead. The cat dose table sets out each one with its duration.
- Administration: Give on an empty stomach whenever possible — absorption is incomplete and concurrent feeding may delay or decrease it. If it causes stomach upset or vomiting, give it with food instead.
- Pharmacokinetics: Rifampin is highly lipophilic and reaches effective concentrations in most tissues including bone, prostate and cerebrospinal fluid, and it penetrates abscesses and caseous material. The elimination half-life in dogs is about 8 hours and shortens by roughly 40% over the first two weeks of treatment as rifampin induces its own metabolism.
- Biofilm activity: Rifampin may have activity against bacteria in biofilms, which may assist treatment of staphylococcal infections on orthopedic implants, although reports in animals are insufficient to confirm clinical effectiveness.
- Laboratory interference: Rifampin interferes with laboratory testing: it can cause false-positive bromosulfophthalein results, it interferes with microbiological assays of serum folate and vitamin B12, and it can cause false-positive results on over-the-counter urine drug tests for opioids.
- Reading a susceptibility report: Susceptibility interpretation is borrowed from human medicine: the CLSI breakpoint is 1.0 mcg/mL and no breakpoint is available for animal isolates, minimum inhibitory concentrations for Gram-positive organisms generally sit around 0.1 mcg/mL, and Gram-negative organisms with MICs of 8 to 32 mcg/mL are considered resistant.
- Storage: Store capsules in a tightly sealed, light-resistant container at room temperature. A compounded 1% oral suspension contains 10 mg/mL and a rifampin suspension mixed with syrup and flavouring is stable for 4 to 6 weeks; reconstituting the 600 mg injection vial produces 60 mg/mL, stable for 24 hours.
