Overview
Excretion methadone decreases with the simultaneous use other drugs that inhibit CYP3A4, such as some drugs for the treatment of HIV infection, macrolides, cimetidine, azole antifungal agents. Methadone Biodone the AUC and Cmax of didanosine and stavudine, reducing the bioavailability of these drugs. In addition, methadone can slow down absorption and increase the effect of the first passage through the liver of the mentioned drugs.
Methadone Increases Plasma Concentration zidovudine for both oral and intravenous administration, and also causes an increase in AUC of zidovudine for oral administration, more treated intravenous administration. Such effects are due to inhibition of zidovudine glucuronidation and a decrease in renal clearance. In this regard, it is necessary to monitor the possible toxicity of zidovudine, and, accordingly, reduce the dosage of zidovudine. Patients who take both drugs may develop typical symptoms of opioid withdrawal syndrome (severe headache, myalgia, fatigue and irritability).
A protease inhibitor can complicate the metabolism of methadone to some extent, but more significant reactions are achieved with ritonavira.
Possible interaction with abacavir no dosage adjustments required.
Efavirenz induces methadone metabolism through the cytochrome P4503A4 system. Therefore, requires dose adjustment.
Methadone Biodone a weak base. Urine Acidifiers (ammonium chloride) may increase renal clearance of methadone, so the dose of methadone should be increased.
The pharmacological action of antagonists (naloxone and naltrexone) is the forte of methadone. These drugs can block the effects of methadone and trigger "withdrawal" syndrome.
Agonists / Antagonists (butorphanol, nalbuphine, pentazocine) can partially block the analgesic effect, respiratory depression and central nervous system depression (CNS) with methadone. Concomitant use can provoke and aggravate forte, respiratory and hypotensive effects. The cumulative or opposite effect depends on the dose of methadone and is becoming more frequent with a low or moderate dose of methadone. These drugs can cause withdrawal symptoms in patients during long-term therapy.
Concomitant use of methadone with drugs, having a depressive effect on the central nervous system may aggravate respiratory depression, therefore, it may be necessary to reduce the ozone of one or both drugs. Disorders on the side of the cardiovascular system can occur in patients simultaneously receiving methadone and drugs, affecting cardiac output or electrolyte balance. In such cases, an ECG is recommended.
Antidiarrheal, antimuscarinic drugs
Diphenoxylate and loperamide can lead to forte cases of constipation, ileum paralysis and aggravation of central nervous system depression, especially with prolonged use.
Octreotide may reduce the analgesic ingredient of morphine and methadone, therefore, if there is a decrease or loss of pain control, the administration of octreotide suspension should be reviewed.
special instructions
Special Risk Patients.
In outpatients, methadone may cause orthostatic hypotension. Methadone should be used with caution with a reduced initial dose in elderly, debilitated patients, patients with hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture. During methadone treatment, prolongation of the QT interval and flutter is possible — ventricular fibrillation, especially when using high doses (> 100 mg / day). Methadone should be used with caution in patients with a risk of lengthening the Look interval, for example, with diseases of the cardiovascular system in the late stage, concomitant treatment with drugs that extend the QT interval in history.
Methadone can cause morphine addiction. As a result of repeated use of methadone, psychophysical dependence and resistance can develop, therefore it should be prescribed and applied with the same caution that is applicable to Biodone
The use of narcotic antagonists.
In individuals with drug-dependent physical dependence, the use of conventional doses of antagonists can cause an acute “withdrawal” syndrome. The severity of the syndrome will depend on the degree of physical dependence and on the dose of the antagonist administered. The use of an antagonist in these subjects may be avoided. If it is necessary to use for the treatment of severe respiratory depression in patients with physical dependence, the antagonist should be used with extreme caution and gradually with doses lower than recommended.
actually with other central nervous system depressants. Methadone should be used with caution and in reduced doses in patients receiving simultaneously other narcotic analgesics, general anesthetics, phenothiazine, other hypnotic sedative tranquilizers, tricyclic antidepressants, and other central nervous system suppressors, including alcohol. In these cases, the development of depression and deep sedation or coma.
Methadone does not have a calming effect, so the symptoms of anxiety that appear during treatment should not be stopped by increasing the dose of methadone.
Traumatic brain injury and increased intracranial pressure.
The ability of methadone to inhibit breathing and increase cerebrospinal fluid pressure can significantly increase in the presence of increased intracranial pressure, and side effects of drugs can mask neurological symptoms in patients with traumatic brain injury (see section “Contraindications”).
Asthma and other diseases of the respiratory Biodone In patients with forte asthma attacks, with chronic obstructive pulmonary disease, pulmonary heart disease, in individuals with a significant decrease in lung volume due to existing respiratory depression, hypoxia or hypercapnia, even usual therapeutic doses of drugs prescribe reduce the activity of the respiratory center and increase airway resistance before onset apnea (see section "Contraindications").
Acute abdominal syndrome.
The use of methadone or other drugs may make it difficult to establish a diagnosis or clinical course in patients with acute abdominal pathology.
The use of methadone can lead to severe hypotension in patients with hypovolemia or concomitant medications, such as phenothiazine or some anesthetics. Methadone may cause orthostatic hypotension.
Using this drug without therapeutic needs is doping. It can give a positive result on doping tests, even at therapeutic doses.