| amphotericin b | it is a naturally occurring polyene macrolide antibiotic produced by Streptomyces nodosus. amphotericin B is the drug of choice for the treatment of life-threatening systemic mycoses.The drug is also sometimes used in combination with flucytosine to achieve more rapid sterilization of the cerebrospinal fluid (CSF) |
| amphotericin mechanism | Several amphotericin B molecules bind to ergosterol in the plasma membranes of sensitive fungal cells.There, they form pores (channels) that require hydrophobic interactions between the lipophilic segment of the polyene antibiotic and the sterol
The pores disrupt membrane function, allowing electrolytes (particularly potassium) and small molecules to leak from the cell, resulting in cell death. its effects on the permeability and transport properties of fungal membranes. Polyenes are molecules with both hydrophilic and lipophilic characteristics (ie, they are amphipathic).
They bind to ergosterol, a sterol specific to fungal cell membranes, and cause
the formation of artificial pores
Resistance, though uncommon, can occur via a decreased level of or a structural change in membrane ergosterol |
| amphotericin use | Amphotericin B is one of the most important drugs available for the treatment of systemic mycoses and is often used for initial induction regimens before follow-up treatment with an azole.
It has the widest antifungal spectrum of any agent and remains the drug of choice, or codrug of choice, for most systemic infections caused by Aspergillus, Blastomyces, Candida albicans, Cryptococcus, Histoplasma, and Mucor.
Local administration of the drug, with minimal toxicity, has been used in treatment of mycotic corneal ulcers and keratitis
Amphotericin B is either fungicidal or fungistatic, depending on the organism and the concentration of the drug. It is effective against a wide range of fungi, including aspergillus, mucor, Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, and many strains of Aspergillus. [Note: Amphotericin B is also used in the treatment of the protozoal infection leishmaniasis.] |
| adverse effects amphotericin | a. Infusion related—Adverse effects related to intravenous infusion commonly include fever, chills, muscle spasms, vomiting, and a shock-like fall in blood pressure. These effects may be attenuated by a slow infusion rate and by premedication with antihistamines, antipyretics, meperidine, or glucocorticoids.
b. Dose limiting—Amphotericin B decreases the glomerular filtration rate and causes renal tubular acidosis with magnesium and potassium wasting. the nephrotoxic effects of the drug are dose-limiting. Dose reduction (with lowered toxicity) is possible in some infections when amphotericin B is used with flucytosine. Liposomal formulations of amphotericin B have reduced nephrotoxic effects, possibly because of decreased binding of the drug to renal cells.
Amphotericin B has a low therapeutic index. The total adult daily dose should not exceed 1.5 mg/kg. Small test doses may be administered to assess the degree of negative responses, such as anaphylaxis or convulsions. A bolus infusion of normal saline before and after amphotericin B infusion may reduce the incidence of drug-induced nephrotoxicity.
Azotemia (elevated blood urea) is exacerbated by other nephrotoxic drugs, such as aminoglycosides, cyclosporine, and pentamidine, although adequate hydration can decrease its severity.
Hypotension: A shock-like fall in blood pressure accompanied by hypokalemia may occur, requiring potassium supplementation. Care must be exercised in patients taking digoxin.
Normochromic, normocytic anemia caused by a reversible suppression of erythrocyte production may occur. This may be exacerbated in patients infected with HIV who are taking zidovudine.
Intrathecal administration can cause a variety of serious neurologic problems.seizures
Thrombophlebitis: Adding heparin to the infusion can alleviate this problem |
| flucocytosine pharmacokinetics | flucytosine passes the CNS
5-FC is well absorbed by the oral route.
5-FU is detectable in patients and is probably the result of metabolism of 5-FC by intestinal bacteria.
Excretion of both the parent drug and its metabolites is by glomerular filtration, and the dose must be adjusted in patients with compromised renal function
The drug is eliminated intact in the urine, and the dose must be reduced in patients with renal impairment. |
| mechanism and resistance of flucytosine | 5-FC enters fungal cells via a cytosinespecific permease, which is an enzyme not found in mammalian cells.
5-FC is then converted by a series of steps to 5-fluorodeoxyuridine 5’ monophosphate.
This false nucleotide inhibits thymidylate synthase, thereby depriving the organism of thymidylic acid, an essential DNA component
The unnatural mononucleotide is further metabolized to a trinucleotide (5-fl uorodeoxyuridine 5’-triphosphate) and is incorporated into fungal RNA, where it disrupts nucleic acid and protein synthesis.
[Note: Amphotericin B increases cell permeability, allowing more 5-FC to penetrate the cell.Thus, 5-FC and amphotericin B are synergistic
Flucytosine is accumulated in fungal cells by the action of a membrane permease and converted by cytosine deaminase to 5-FU, an inhibitor of thymidylate synthase
Selective toxicity occurs because mammalian cells have low levels of permease and deaminase.
Resistance can occur rapidly if flucytosine is used alone and involves decreased activity of the fungal permeases or deaminases. When 5-FC is given with amphotericin B, or triazoles such as itraconazole, emergence of resistance is decreased and synergistic antifungal effects may occur |
| use of flucytosine | the antifungal spectrum of 5-FC is narrow; used in combination with amphotericin B or a triazole, of infections resulting from Cryptococcus neoformans, possibly systemic candidal infections and chromoblastomycosis caused by molds
5-FC is fungistatic. It is effective in combination with itraconazole for treating chromoblastomycosis and in combination with amphotericin B for treating candidiasis and cryptococcosis. |
| flucytosine toxicity | Prolonged high plasma levels of flucytosine cause dose related reversible bone marrow depression, alopecia. 5-FC causes reversible neutropenia, thrombocytopenia. Caution must be exercised in patients undergoing radiation or chemotherapy with drugs that depress bone marrow. Reversible hepatic dysfunction with elevation of serum transaminases and alkaline phosphatase may occur. nausea, vomiting, and diarrhea, are common, and severe enterocolitis may also occur.
[Note: Some of these adverse effects may be related to 5-FU formed by intestinal organisms from 5-FC.] |
| azole mechanism | Azoles are predominantly fungistatic. They inhibit C-14 α-demethylase (a cytochrome P450 [CYP450] enzyme), thereby blocking the demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes
This inhibition disrupts membrane structure and function, which, in turn, inhibits fungal cell growth
[Note: Unfortunately, as is often the case for the initial member of a class of drugs, the selectivity of ketoconazole toward its target is not as precise as those of later azoles. For example, in addition to blocking fungal ergosterol synthesis, the drug also inhibits human gonadal and adrenal steroid synthesis, leading to decreased testosterone and cortisol production. In addition,
ketoconazole inhibits CYP450-dependent hepatic drug-metabolizing enzymes.]
With increasing use of azole antifungals, especially for long-term prophylaxis in immunocompromised and neutropenic patients, resistance is occurring, possibly via changes in the sensitivity of the target enzymes. |
| uses ketoconazole | Oral ketoconazole is active against many fungi, including Histoplasma, Blastomyces, Candida, and Coccidioides
Itraconazole has largely replaced ketoconazole in the treatment of most mycoses because of its broader spectrum, greater potency, and fewer adverse effects.
As a second-line drug, oral ketoconazole is a less-expensive alternative for the treatment of mucocutaneous candidiasis.
However, strains of several fungal species that are resistant to ketoconazole have been identified.
Topical ketoconazole is used to treat tinea corporis, tinea cruris, and tinea pedis caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. Also, topical ketoconazole is used to treat tinea versicolor caused by Malassezia furfur,cutaneous candidiasis caused by Candida species.
It is also used topically in the treatment of seborrheic dermatitis and dandruff
for chronic mucocutaneous candidiasis and is also effective against dermatophytes |
| ketoconazole pharmacokinetics | When ketoconazole is administered orally, it requires gastric acid for dissolution and is absorbed through the intestinal mucosa.
Drugs that raise gastric pH, such as antacids, or that interfere with gastric acid secretion, such as H2-histamine– receptor blockers and proton-pump inhibitors, impair absorption.
Administering acidifying agents, such as cola drinks, before taking the drug can improve absorption in patients with achlorhydria.
Ketoconazole is extensively bound to plasma proteins.
Although penetration into tissues is limited, it is effective in the treatment of
histoplasmosis in lung, bone, skin, and soft tissues. The drug does not enter the CSF. Extensive metabolism occurs in the liver, and excretion is primarily through the bile. Levels of parent drug in the urine are too low to be eff ective against mycotic infections of the urinary tract. |
| ketaconazole toxicity | In addition to allergies, dose-dependent gastrointestinal disturbances, including nausea, anorexia, and vomiting, are the most common adverse effects of ketoconazole treatment.
Endocrine effects, such as gynecomastia, decreased libido, impotence, and menstrual irregularities, result from the blocking of androgen and adrenal steroid synthesis by ketoconazole.
Transient increases in serum transaminases occur in 2 to 10 percent of patients
receiving ketoconazole.Frank hepatitis occurs rarely, but requires immediate cessation of ketoconazole treatment.[Note: Ketoconazole may accumulate in patients with hepatic dysfunction.Plasma concentrations of the drug should be monitored in these individuals.]immediate cessation of ketoconazole treatment. [Note: Ketoconazole may accumulate in patients with hepatic dysfunction. Plasma concentrations of the drug should be monitored in these individuals.]By inhibiting CYP450, ketoconazole can potentiate the toxicities of drugs such as cyclosporine, phenytoin, triazolam, and warfarin, among others
Rifampin, an inducer of the CYP450 system, can shorten the duration of action of ketoconazole and the other azoles.
Drugs that decrease gastric acidity, such as H2-receptor blockers, antacids, proton-pump inhibitors, and sucralfate, can decrease absorption of ketoconazole. Ketoconazole and amphotericin B should not be used together, because the decrease in ergosterol in the fungal membrane reduces the fungicidal action of amphotericin B
ketoconazole is teratogenic |
| fluconazole uses | Fluconazole is employed prophylactically, with some success, for reducing fungal infections in recipients of bone marrow transplants.
It inhibits the synthesis of fungal membrane ergosterol in the same manner as ketoconazole
drug of choice for Cryptococcus neoformans after therapy with amphotericin B, for most candidemias, and for coccidioidomycosis. most forms of mucocutaneous candidiasis.
Treatment failures due to resistance have been reported in some HIVinfected patients.]
For the treatment of vaginal candidiasis, the dose is 150 mg as a single oral dose.
Fluconazole is a drug of choice in esophageal and oropharyngeal candidiasis and for most infections caused by Coccidioides. A single oral dose usually eradicates vaginal candidiasis.
Fluconazole is a drug of choice in esophageal and oropharyngeal candidiasis and for most infections caused by Coccidioides.
The drug is also equivalent to amphotericin B in candidemia |
| ciclopirox | Ciclopirox inhibits the transport of essential elements in the fungal cell, disrupting the synthesis of DNA, RNA, and protein.
Ciclopirox is active against Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, Candida albicans, and Malassezia furfur.
Ciclopirox 1% shampoo is used for treatment of seborrheic dermatitis.
Ciclopirox 0.77% gel is used for treatment of interdigital tinea pedis, tinea corporis, and seborrheic dermatitis.
Ciclopirox 8% solution is used for treatment of onychomycosis of nails without lanula involvement.
Ciclopirox 0.77% cream and suspension is used for treatment of dermatomycosis, candidiasis, and tinea versicolor. |
| tolnaftate | Tolnaftate distorts the hyphae and stunts mycelia growth in susceptible fungi. Tolnaftate is active against Epidermophyton, Microsporum, and Malassezia furfur. [Note: Tolnaftate is not effective against Candida.] Tolnaftate is used to treat tinea pedis, tinea cruris, and tinea corporis. It is available as a 1% solution, cream, and powder. |
| fluconazole | Fluconazole is a member of the triazole class of antifungal products.
its lack of the endocrine side effects of ketoconazole and its excellent penetrability into the CSF of both normal and inflamed meninges.
Fluconazole is administered orally or intravenously.
Its absorption is excellent and, unlike that of ketoconazole, is not dependent on gastric acidity. Binding to plasma proteins is minimal.Unlike ketoconazole, fluconazole is poorly metabolized. The drug is excreted via the kidney, and doses must be reduced in patients with compromised renal function.
The adverse effects caused by fluconazole treatment are less of a problem than those with ketoconazole.
Fluconazole has no endocrinologic effects because it does not inhibit the CYP450 system responsible for the synthesis of androgens. However, it can inhibit the P450 cytochromes that metabolize other drugs listed
Nausea, vomiting, and rashes are a problem. There is a caution for patients with liver dysfunction.
Fluconazole is teratogenic, as are other azoles, and should not be used in pregnancy. |
| nyastatin | Nystatin is a polyene antibiotic, and its structure, chemistry, mechanism of action, and resistance profile resemble those of amphotericin B.
Its use is restricted to topical treatment of Candida infections because of its systemic toxicity.
The drug is negligibly absorbed from the gastrointestinal tract
It is administered as an oral agent (“swish and swallow” or “swish and spit”) for the topical treatment of oral candidiasis. Excretion in the feces is nearly quantitative. Adverse effects are rare because of its lack of absorption orally, but nausea and vomiting occasionally occur that disrupts fungal membranes by binding to ergosterol.
Nystatin is commonly used topically to suppress local Candida infections and has
been used orally to eradicate gastrointestinal fungi in patients with impaired defense mechanisms.
Other topical antifungal agents that are widely used include the azole compounds miconazole, clotrimazole, and several others |
| azoles | The azoles other than voriconazole and posaconazole are commonly used orally for the treatment of dermatophytoses.
Pulse or intermittent dosing with itraconazole is as effective in onychomycoses as continuous dosing because the drug persists in the nails for several months. Typically, treatment for 1 wk is followed by 3 wk without drug.
Advantages of pulse dosing include a lower incidence of adverse effects and major cost savings.
Topical forms of various azoles are also available for use in dermatophytoses
Imidazoles are azole derivatives, they have a wide range of activity against Epidermophyton, Microsporum, Trichophyton, Candida albicans, and Malassezia furfur, depending on the agent.
Topical use is associated with contact dermatitis, vulvar irritation, and edema
Miconazole is a potent inhibitor of warfarin metabolism and has produced bleeding in warfarin-treated patients even when applied locally to the vaginal area.
No significant difference in clinical outcomes is associated with any azole or nystatin in the treatment of vulvar candidiasis |
| itraconazole | Itraconazole is an antifungal agent with a broad antifungal spectrum. Like fluconazole, it is a synthetic triazole Its mechanism of action is the same as that of the other triazoles.
Itraconazole is the drug of choice for the treatment of blastomycosis, sporotrichosis, paracoccidioidomycosis, and histoplasmosis by Blastomyces and Sporothrix and for subcutaneous chromoblastomycosis.
Itraconazole is an alternative agent in the treatment of infections caused by Aspergillus, Coccidioides, Cryptococcus, and Histoplasma.
In esophageal candidiasis, the drug is active against some strains resistant to fluconazole. Itraconazole is also used extensively in the treatment of dermatophytoses, especially onychomycosis
Itraconazole is well absorbed orally, but it requires acid for dissolution. Food increases the bioavailability of some preparations.
The drug is not attained in the CSF.Like ketoconazole, itraconazole is extensively metabolized by the liver, but it does not inhibit androgen synthesis. Its major metabolite, hydroxyitraconazole, is biologically active, with a similar antifungal spectrum. Little of the parent drug appears in the urine, eliminating the need for dose reduction with renal failure.Adverse effects include nausea and vomiting, rash (especially in ic patients), hypokalemia, hypertension, edema, and headache. Itraconazole should be avoided in pregnancy.
Itraconazole inhibits the metabolism of many drugs, including oral anticoagulants, statins, and quinidine. Inducers of the CYP450 system increase the metabolism of itraconazole. The capsules should not be taken by patients with evidence of ventricular dysfunction, such as congestive heart failure (CHF) or a history of CHF |
| butenafine | Butenafine is active against Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Malassezia furfur.
Butenafine 1% cream is used for topical treatment of tinea corporis, tinea cruris, interdigital tinea pedis, and tinea versicolor. |
| naftifine | Naftifine is active against Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Epidermophyton floccosum. Naftifine 1% cream and gel is used for topical treatment of tinea corporis, tinea cruris, and tinea pedis. |
| squalene oxidase inhibitors | These agents act by inhibiting squalene epoxidase, resulting in the
blocking of the biosynthesis of ergosterol, an essential component of
fungal cell membrane. |
| micafungin and anidulafungin | Micafungin and anidulafungin are the newer members of the echinocandins class of antifungal drugs.
Micafungin and anidulafungin have similar efficacy against Candida species, but the efficacy for treatment of other fungal infections has not been established. The dose of micafungin and anidulafungin does not need to be adjusted in renal impairment or mild-to-moderate hepatic dysfunction.
The half-life of micafungin is slightly longer, and that of anidulafungin is 24–48 h.
Micafungin does not require a loading dose.
Micofungin is used for mucocutaneous candidiasis and for prophylaxis of Candida infections in bone marrow transplant patients.
Micafungin also causes histamine release and elevates blood levels of the immunosuppressant drugs cyclosporine and sirolimus.
Micofungin is used for mucocutaneous candidiasis and for prophylaxis of Candida infections in bone marrow transplant patients. |
| terabinafine uses | Oral terbinafine is the drug of choice for treating dermatophytoses and, especially, onychomycoses (fungal infections of nails). It is better tolerated, requires shorter duration of therapy, and is more effective than either itraconazole or griseofulvin Terbinafine inhibits fungal squalene epoxidase,thereby decreasing the synthesis of ergosterol This plus the accumulation of toxic amounts of squalene result in the death of the fungal cell. [Note: Significantly higher concentrations of terbinafine are needed to inhibit human
squalene epoxidase, an enzyme required for the cholesterol synthetic pathway.]
Topical terbinafine is active against Trichophyton rubrum and Trichophyton mentagrophytes .
It may also be effective against Candida albicans, Epidermophyton floccosum,and Scopulariopsis brevicaulis, but the safety and efficacy in treating clinical
infections due to these pathogens has not been established.Topical terbinafine 1% cream and solution are used to treat tinea pedis, tinea corporis, and tinea cruris. Therapy is prolonged (usually about 3 months) but considerably shorter than that with griseofulvin |
| terabinafine adverse effects | Terbinafine is available in both oral and topical forms.
Adverse effects include gastrointestinal upsets, rash, headache, and taste disturbances,diarrhea, dyspepsia, and nausea
although its bioavailability is only 40 percent due to first-pass metabolism. Terbinafine is greater than 99 percent bound to plasma proteins. It is deposited in the skin, nails, and fat.
Terbinafine accumulates in breast milk and should not be given to nursing mothers. A prolonged terminal half-life of 200 to 400 hours may reflect the slow release from these tissues.
Oral terbinafine is extensively metabolized prior to urinary excretion Patients with either moderate renal impairment or hepatic cirrhosis have reduced clearance.
Taste and visual disturbances have been reported as well as transient elevations in serum liver enzyme levels.
Rarely, terbinafine may cause hepatotoxicity and neutropenia.
Rifampin decreases blood levels of terbinafine, whereas cimetidine increases blood levels |
| caspofungin | Used intravenously, the drugs distribute widely to the tissues and are eliminated largely via hepatic metabolism. Caspofungin has a half-life of 9–12 h.
The echinocandins, inhibiting the synthesis of β(1-3)glucan, a critical component of fungal cell walls
Caspofungin is used for disseminated and mucocutaneous Candida infections in patients who fail to respond to amphotericin B and in the treatment of mucormycosis.
Anidulafungin is used for esophageal and invasive candidiasis.
Infusion-related effects of caspofungin include headache, gastrointestinal distress, fever, rash,phlebitis and flushing (histamine release). Combined use of echinocandins with cyclosporine may elevate liver transaminasescaspofungin is the first approved member of the echinocandins class of antifungal drugs.Caspofungin has activity against Aspergillus and most Candida species, including those species resistant to azoles.
Flushing occurs, which is probably due to the release of histamine from mast cells
.Concomitant administration of caspofungin with CYP450 enzyme inducers may require an increase in the daily dose administered. Caspofungin should not be coadministered with cyclosporine.
Caspofungin is a second-line antifungal for those who have failed or cannot tolerate amphotericin B or an azole. |
| voriconazole | Voriconazole a triazole, has the advantage of being a broad-spectrum antifungal agent.
It is available for both IV and oral administration and is approximately 96 percent bioavailable.
Voriconazole penetrates tissues well, including the CNS.
Elimination is primarily by metabolism through the CYP450 2C19, 2C9, and 3A4 enzymes.
Voriconazole has an even wider spectrum of fungal activity than itraconazole. |
| voriconazole uses | Voriconazole is approved for the treatment of invasive aspergillosis and has replaced amphotericin B as the treatment of choice for this indication.
Voriconazole is also approved for treatment of serious infections caused by Scedosporium apiospermum and Fusarium species.
It is a codrug of choice for treatment of invasive aspergillosis; some studies report greater efficacy than amphotericin B.
Voriconazole is an alternative drug in candidemia with activity against some fluconazole-resistant organisms and in AIDS patients has been used in the treatment of candidial esophagitis and stomatitis |
| voriconazole side effects | The significant number of drug interactions due to its metabolism through the various hepatic enzymes may limit its use.
Side effects are similar to those of the other azoles. High trough concentrations are associated with visual and auditory hallucinations |
| posaconazole mechanism and use | The broadest-spectrum triazole, posaconazole has activity against most species of Candida and Aspergillus.
It is the only azole with activity against Rhizopus, one of the agents of mucormycosis and is used for prophylaxis of fungal infections during cancer chemotherapy and in salvage therapy in invasive aspergillosis.
Due to its spectrum of activity, posaconazole could possibly be used in the treatment of fungal infections caused by Mucor species and other zygomycetes.
Due to its inhibition of CYP450 3A4 enzymes, posaconazole may increase the effect and toxicity of many drugs, including cyclosporine, tacrolimus, and sirolumus. |
| posconazole adverse effect | The most common side effects observed were gastrointestinal issues (nausea, vomiting, diarrhea, and abdominal pain) and headaches.
Like other azoles, posaconazole can cause an elevation of the liver function tests, causing elevated serum levels of hepatic transaminases.
Additionally, in patients who are receiving concomitant cyclosporine or tacrolimus for management of transplant rejection, rare cases of hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and pulmonary embolus have been reported.
Concomitant use of posaconazole with ergot alkaloids, pimozide, and quinidine is contraindicated. |
| pharmacokinetics poconazole | To be effective, posaconazole must be administered with a high fat meal. Posaconazole may be given two or four times daily for a total daily dose of 800 mg of mucormycosis and is used for prophylaxis of fungal infections during cancer chemotherapy and in salvage therapy in invasive aspergillosis.Used intravenously, the drugs distribute widely to the tissues and are eliminated largely via hepatic metabolism. |
| griseofulvin use | Griseofulvin has been largely replaced by oral terbinafine for the treatment of dermatophytic infections of the nails, although it is still used for ringworm and dermatophytosis of the skinand hair.
It is only fungistatic. |
| griseofulvin mechanism | Griseofulvin accumulates in newly synthesized, keratin-containing tissue, where it causes disruption of the mitotic spindle and inhibition of fungal mitosis Duration of therapy is dependent on the rate of replacement of healthy skin and nails.
Ultrafine crystalline preparations are absorbed adequately from the gastrointestinal tract, and absorption is enhanced by high-fat meals. Griseofulvin induces hepatic CYP450 activity. It also increases the rate of metabolism of a number of drugs, including anticoagulants. It may exacerbate intermittent porphyria
Oral absorption of griseofulvin depends on the physical state of the drug—ultra-micro-size formulations, which have finer crystals or particles, are more effectively absorbed—and is aided by high-fat foods.
Griseofulvin requires treatment of 6 to 12 months in duration.
The drug is distributed to the stratum corneum, where it binds to keratin. Biliary excretion is responsible for its elimination. |
| griseofulvin adverse effect | Griseofulvin interferes with microtubule function in dermatophytes) and may also inhibit the synthesis and polymerization of nucleic acids. Sensitive dermatophytes take up the drug by an energy-dependent mechanism, and resistance can occur via decrease in this transport. The oral formulation of the drug is indicated
Adverse effects include headaches, mental confusion, gastrointestinal irritation, photosensitivity, and changes in liver function. Griseofulvin should not be used in patients with porphyria. Griseofulvin decreases the bioavailability of warfarin, resulting in decreased anticoagulant effect, and it also causes disulfiram-like reactions with ethanol |
