drugs

Ketoconazole

Ketoconazole (or ketoconazole) is an antifungal drug belonging to the class of azole-type antifungals.

Ketoconazole - Chemical Structure

Ketoconazole is used to treat cutaneous fungal infections, but is also used in the treatment of Cushing's syndrome, a syndrome characterized by excessive levels of glucocorticoid hormones - in particular cortisol - in the body.

Ketoconazole is available as shampoo, skin cream and tablets for oral use.

Indications

For what it uses

Ketoconazole in the form of shampoo is indicated for the treatment of:

  • Seborrheic dermatitis;
  • Dandruff (Pityriasis capitis).

Ketoconazole in skin cream, on the other hand, is indicated for the treatment of cutaneous mycoses of various kinds, including:

  • Cutaneous candidiasis;
  • Tinea versicolor;
  • Tinea corporis;
  • Tinea manus;
  • Tinea pedis;
  • Tinea cruris;
  • Seborrheic dermatitis.

Oral ketoconazole, on the other hand, is indicated for the treatment of Cushing's syndrome.

Warnings

The use of ketoconazole based shampoo is not indicated in infants and children.

Before starting treatment with the ketoconazole based skin cream, it is advisable to inform your doctor if you are in one of the following situations:

  • If you suffer from liver problems;
  • If in the past a therapy based on griseofulvin (another antifungal) was performed;
  • If you are using skin care products containing steroid drugs (such as betamethasone or hydrocortisone).

Should sensitization occur during ketoconazole therapy for cutaneous use, treatment with the drug should be immediately suspended.

During treatment with ketoconazole orally, the liver and adrenal function of patients must be constantly monitored. If symptoms such as weakness, fatigue, lack of appetite, nausea, vomiting or hypotension occur, contact your doctor immediately.

Oral ketoconazole may cause abnormal heart rhythm. In the event of palpitations, contact your doctor immediately.

Oral ketoconazole should not be used in children under 12 years of age.

Finally, oral ketoconazole can cause side effects that can alter the ability to drive and / or use machinery, so great care should be taken.

Interactions

There are no known drug interactions between ketoconazole for skin use and other drugs. However, before starting treatment with ketoconazole for cutaneous use, it is necessary to have completed any other treatments based on steroid drugs (such as betamethasone or hydrocortisone ).

Before starting treatment with ketoconazole orally, instead - due to the possible harmful effects that could occur - you need to inform your doctor if you are already taking any of the following drugs:

  • Oral anticoagulants ;
  • Antivirals used in the treatment of HIV, such as, for example, ritonavir;
  • Some anticancer drugs, such as docetaxel, erlotinib, imatinib, sunitinib, paclitaxel, vincristine, etc .;
  • Some antibiotics, such as clarithromycin or rifampicin;
  • Antidiabetic drugs;
  • Antipsychotic drugs;
  • Antihypertensive drugs;
  • Antiarrhythmic drugs;
  • Antiepileptics ;
  • Some glucocorticoids ;
  • Opioid analgesics ;
  • Antiemetics (ie antivomito drugs);
  • Drugs for erectile dysfunction ;
  • Migraine medications ;
  • Antihistamines ;
  • Immunosuppressive drugs .

In any case, it is still necessary to inform your doctor if you are taking - or if you have recently been - medicines of any kind, including over-the-counter drugs and herbal and / or homeopathic products.

Side effects

Ketoconazole can cause various types of side effects, although not all patients experience them.

The type of adverse effects and the intensity with which they occur depend on the different sensitivity that each individual has towards the drug.

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

Pathologies of the central nervous system

Treatment with ketoconazole orally may cause:

  • Headache;
  • Drowsiness;
  • Fatigue;
  • dizziness;
  • Anorexia;
  • Loss or increase in appetite;
  • Tingling or tingling sensation.

Psychiatric disorders

Treatment with oral ketoconazole can cause insomnia and nervousness.

Gastrointestinal disorders

Oral ketoconazole therapy may cause:

  • Nausea;
  • He retched;
  • Diarrhea;
  • Abdominal pain;
  • Dyspepsia;
  • Flatulence.

Hepatobiliary disorders

Treatment with oral ketoconazole can cause an increase in blood levels of liver enzymes and promote the onset of jaundice.

Other side effects

Other side effects that may occur during oral ketoconazole therapy are:

  • Allergic reactions, even serious, in sensitive subjects;
  • Muscle weakness;
  • Malaise;
  • Adrenal insufficiency;
  • Palpitations;
  • Hot flashes;
  • Menstrual disorders;
  • Erectile dysfunction;
  • azoospermia;
  • Gynecomastia;
  • Temporary decrease in testosterone production;
  • Skin eruptions;
  • Urticaria;
  • Itch;
  • Decrease in the number of platelets in the bloodstream;
  • Hair loss.

Side effects that can occur with the use of ketoconazole based shampoo

Using the ketoconazole based shampoo can cause side effects, such as:

  • Allergic reactions in sensitive individuals;
  • Angioedema;
  • Urticaria;
  • Alterations in the sense of taste;
  • Dryness of the skin;
  • Blistering on the skin;
  • Local irritation, itching or redness;
  • Hair loss;
  • Dry and brittle hair;
  • Hair discoloration;
  • folliculitis;
  • Eye irritation;
  • Increased tearing;
  • Pustule formation at the site of administration.

Side effects that can occur with the use of ketoconazole-based cream

Ketoconazole cream therapy may cause side effects, such as:

  • Allergic reactions in sensitive patients;
  • Redness, itching, burning, dryness, discomfort and / or loss of sensitivity at the site of application of the cream;
  • Appearance of skin lesions;
  • Sticky skin;
  • Urticaria.

Overdose

If excessive doses of ketoconazole are used for skin use, swelling, itching or burning may occur.

In case of accidental ingestion of ketoconazole for cutaneous use or in case of an overdose of ketoconazole for oral use, it is necessary to immediately inform the doctor and contact the nearest hospital.

Action mechanism

Ketoconazole is an azole antifungal that exerts its action by interfering with the synthesis of ergosterol.

Ergosterol is a sterol contained in the plasma membrane of fungal cells.

Ketoconazole is able to inhibit one of the key enzymes of the synthesis of the aforementioned ergosterol: 14α-demethylase.

By inhibiting 14α-demethylase, the precursors of ergosterol begin to accumulate within the fungal cell. When they reach too high cellular concentrations, these precursors become toxic for the same cell and, moreover, they cause alterations in the permeability of the cell membrane and alterations in the functioning of the proteins contained in it. The fungal cell is thus condemned to certain death.

Furthermore, ketoconazole is effective in the treatment of Cushing's syndrome. This syndrome is characterized by excessive production of glucocorticoids (in particular cortisol) by the body.

Ketoconazole is able to inhibit the enzymes involved in cortisol synthesis, thus reducing its levels in the body. In this way, there is an improvement in the symptoms of Cushing's syndrome.

Mode of Use - Posology

As previously mentioned, ketoconazole is available in different pharmaceutical forms (shampoo, cream and tablets) for the treatment of various diseases.

Regardless of the chosen pharmaceutical formulation and the type of pathology to be treated, during the ketoconazole-based therapy it is essential to follow scrupulously the indications provided by the doctor, both as regards the amount of drug to be used, and as regards the duration of treatment.

Below are some indications on the doses of ketoconazole usually used in therapy.

Treatment of seborrheic dermatitis and dandruff

Ketoconazole-based shampoo is used for the treatment of seborrheic dermatitis and dandruff.

It is advisable to use the shampoo twice a week, for a period of 2-4 weeks.

For the prevention of recurrences, instead, it is recommended to use the shampoo once a week, or once every two weeks.

Treatment of cutaneous mycoses

For the treatment of different types of cutaneous mycoses (see paragraph "Therapeutic indications") the ketoconazole based skin cream is used.

We recommend applying the cream 1-2 times a day for a period ranging from two to six weeks. The number of applications and the duration of treatment depend on the type and severity of the fungal infection that must be treated.

Treatment of Cushing's syndrome

Ketoconazole is used orally for the treatment of Cushing's syndrome.

The recommended starting dose is 600 mg of ketoconazole per day, to be taken in three divided doses.

In any case, the doctor will determine the most suitable dose for each individual patient by performing appropriate analyzes, both before starting treatment with the drug and for the duration of the drug.

Pregnancy and breastfeeding

Ketoconazole in the form of shampoo or skin cream can be used both during pregnancy and during breastfeeding. However, pregnant women and breastfeeding mothers should still consult their doctor before using the aforementioned ketoconazole preparations.

Oral ketoconazole, on the other hand, should not be used in pregnant women and breastfeeding mothers due to the damage that the drug can cause to the fetus or baby.

Contraindications

The use of ketoconazole topically is contraindicated in patients with known hypersensitivity to ketoconazole itself.

Oral ketoconazole, on the other hand, is contraindicated in the following cases:

  • In patients with known hypersensitivity to ketoconazole itself;
  • In patients with heart rhythm abnormalities;
  • Pregnant;
  • During breastfeeding.