These medications include
|Recently a question from another forum member prompted me to post this refresher about medications that interact with methadone. To read the complete article about medications that interact with methadone please click the link|
Some medications initially interact with methadone to cause sedation, but then the opposite occurs, and they can cause withdrawal symptoms. May cause additive CNS depression.
: 1. Benzodiazepines such as
Xanax®- Diazepam -- Valium®Clorazepate Dipotassium
-- Apo-Clorazepate®, Gen-XENE®, Novoclopate®, Tranxene® , Tranxene-SD®, Tranxene-T-Tab® Estalozam--
--Versed® is mostly used as an injection for sedation before surgical procedures.Triazolam
Restoril® Prazepam --
|Alcohol is an extremely potent central nervous system depressant. Please use it wisely when taking in combination with other medication. |
-- Ethyl alcohol is an extremely potent central nervous system depressant. If alcoholic beverages are taken with drugs such as antiseizure medications, antipsychotics, antidepressants, and similiar drugs that produce central nervous system depression
, particularly barbiturates, which can be lethal by themselves if abused , the central and autonomic nervous can be depressed to an extent that they are unable to function. Since the depressant effect is so much greater when both drugs are taken concurrently
, this is a synergistic reaction. Barbiturate sedatives and/or hynotics taken with methadone , if both drugs are taken concurrently will produce a synergistic action, as described above. P450 enzyme induction. (Kreek 1986); phenobarbital can cause sharp decrease in methadone (Gourevitch 2001) . Methadose dose increase usually required
Barbiturate sedatives and/or hynotics taken with methadone , if both drugs are taken concurrently will produce a synergistic action, as described above. P450 enzyme induction. (Kreek 1986); phenobarbital can cause sharp decrease in methadone (Gourevitch 2001) . Methadose dose increase usually required.
3. Barbiturates include the following:
Luminal Sodium® --- Phenobarbital Sodium Phenobarbital can cause sharp decrease in methadone.
Seconal® --- Secobarbital Sodium Nembutal® --- Pentobarbital
Tuinal® --- Amobarbital/Secobarbital
Aprobarbital® --- No Trade Names Mebaral® --- Mephobarbital
Butalbital --- Bancap®, Axotal®, Butal Compound®, Bucet®, Fiorcet®, Fiorinal®, Fiorinal #3®
Butabarbital --- Butalan®, Butacaps®, Sarisol® Butisol®
4. Some medicines slow the metabolism of methadone.
Sometimes people will feel the effect of methadone more strongly when they take these medications, and sometimes they experience withdrawal symptoms when they stop taking these medications:
Antidepressants include the following: (Tricyclic Antidepressants) Possible increased TCA toxicity; uncertain effect on methadone; increase or decrease.
Amitriptyline - Elavil® Desipramine - Norpramin®
Imipramine - Tofranil® Nortriptyline - Pamelor®
The drugs may not be all-inclusive of drugs/brands that might be contraindicated or interact with methadone. .
H2-receptor antagonist for GI disorders:
---Prilosec® Treatment of acid-related GI disorders. In animal studiies, possibly affects methadone absorption (Strang 1999). Selective Serotonin Uptake Inhibitors-
affect chemicals in the brain that have become unbalanced and cause obsessive -compulsive disorder; used to treat obsessive-compulsive disorders involving reoccuring thoughts and actions;can be used for depression.
Sertraline-Zoloft®Antifungal Antibiotic Fluconazole
|Warning!!! The drugs listed below may|
raise serum methadone levels and/or
increase the effects of the ................
methadone. Your dose of methadone
may need to be lowered temporarily.
Cipro® Quinolone AntibioticMacrolide Antibiotics-
Predicted due to strong inhibition of CYP3A4 enzyme. Cardiac and metabolic effects not expected with azithromycin (Eap et al. 2002). Anti-infective.Erythromycin-
EES® Erythrocin® Clarithromycin-
TAO® Antibiotic (similiar to erythromycin).Urinary Alkalinizers
-Treatment of kidney stones, gout therapy. Alkaline (higher pH) decreases methadone excretion by kidneys
. (Kalvik et al. 1996). Sodium Bicarbonate
- Sedation noticed with higher doses of disulfiram (Bochner 2000).Disulfiram-
Antibuse®Ethanol - Acute Use
(Euphoric, sedative) Competition for P450 enzymes (Quinn et al.)
Wine, beer, Whiskey...Migraine Treatment -
CYP3A4 enzyme inhibition (Van Beusekom and Iguchi 2000),Dihydroergotamine -
Valium®, Dizac®, Valrelease® Control of anxiety and stress. Mechanism undetermined (Eap et al. 2002) and effect sporadic (Levy et al. 2000).Grapefruit-
juice or whole fruit Inhibits intestinal CYP3A4 (Hall et al. 1999) and PgP (Eap. et al. 2002i) This effect is not expected with other fruits/juices
(Karlix 1990."natural' supplements"
-Herbal products used for gastrointestinal therapy, Immune system enhancement, others. Not stuidied specifically with methadone; predicted potential effect due to strong CYP3A4 enzyme inhibition (Scott and Elmer 2002, Van Beusekson and Iguchi 2001).Uncaria tomentosa
-Cat's claw ® Matriacaria recutita
Echinacea® Hydrastis canadensis
May be ungredient in various product brands).Delavirdine-
Rescriptor® NNRTI antiretroviral Predicted effect due to CYP3A4 enzyme inhibition (Gourevitch 2001).Mocloemide -
Auroxix®,Manerix® MAO Inhibitor (antidepressant)
Expected due to CYP2D6 and/or CYP1A2 Inhibitio (Eap et al. 2002).Verapamil -
Calan®, Covera-HS®, Isoptin® Cardiac drug; Ca++ -blocker. Predicted effect due to CYP450 enzyme inhibition.
|The medications below cause the liver |
to metabolize methadone more quickly
and may cause a need for an increased
News Alert!!! May need to raise dose
temporarily--see your physician if with-
) - Ziagen® NRTI antiretoviral
Methadone level decreased; also reduces ABC peak concentration (Gourevitch 2001).Amprenavir -
Agenerase® Pl antiretroviral
CYP3A4 enzyme induction may decrease methadone levels (Chrisman 2003;Eap; et al.2002). Amprevair also may be reduced. (Faragon and Piliero 2003). Carbamazepine
- Atrotol® Tegretol® Anticonvulsant for epilepsy and trigeminal neuralgia.
Strong CYP3A4 enzyme induction may cause withdrawal. Effect not predicted with valproate
(Depakote; Bochner 2000; Saxon et al. 1989). Cocaine
- Crack,coke,others Illicit Stimulant
Accelerates methadone elimination (Moolchan et al.).Dexamethasone -
Decadron® Hexadrol® Corticosteroid
CYP3A4 enzyme inducer (Eap et al. 2002).Efavirenz
- Sustiva® NNRTI Antitetroviral
Due to CYP3A4 induction; methadone withdrawal is common and dose increase usually required (Eap et al.2002, McCance- Katz et al. 2002).Ethanol
.- (Chronic Use)
wine, beer, whiskey Euphoric, sedative
P450 enzyme induction. (Quinn et al. 1997).Fusidic acid - (systemic steroidal
CYP3A4 enzyme induction (Eap et al. 2002; Van Beusekom and Iguchi2001).Heroin -
smack, scat, others Illicit Opioid
Decreases free faction of methadone.Lopinavir + Ritonavir -
Kaletra® PI antiretroviral Withdrawal symptoms may occur requiring methadose dose increase.
Latest research suggests effect is not seen with ritonnavir (Chrisman 2003; McCance - Katz et al. ). Nelfinavir -
Viracept® Pl antiretroviral
CYP3A4 and PgP induction (Eap et al.2002) but clinical withdrawal is rare (McCance-Katz et al. in press 2003) Interaction also may mildly decrease nelfinavir (Chrisman 2003).Nevirapine -
Viramune® NNRTI antiretroviral
CYP3A4 enzyme induction may precipitate opioid withdrawal.Phenytoin -
Dilantin® Control of seizures.
Sharp decrease in methadone due to CYP3A4enzyme induction (Eap. et al. 2002).Rifampin (rifampicin) and rifampin/isoniazid -
Rifadin®, Rimactane®, Rifamate® Treatment of pulmonary tuberculosis.
Induces P450 enzymes; cases of severe withdrawal reported (Eap et al. 2002; Kreek 1986). Effext not seen with rifabutin (Mycobutin: Gourevitch 2001; Levy et al. 2000).Spironolactone -
Aldactone® K+ sparing diuretic
CYP3A4 induction (Eap et al. 2002).St. John's wort (Hypericum perforatum) -
Ingredient in various OTC products. Herb used as antidepressant.
Induces CYP3A4; 47% decrease in methadone (Eich-Hochli et al. 2003; Scot and Elmer 2002).Tobacco
- various brands Habitual smoking. ( some mixed reports, but most indicate reduced effectiveness of methadone
(Moolchan et al. 2001; Tacke et al. 2001)Urinary Acidifiers (Ascorbic Acid) - Vitamin C (large doses); K-Phos Dietary supplement; keeps calcium soluble. Methadone is excreted by kidneys more rapidly at a lower pH
(Nillson et al.1982; Strang 1999).
Didanosine (ddl, buffered tablet) -
|May result in altered metabolism or |
unpredictable interactions in com-
bination with methadone.
Videx® NRTI antiretroviral
Decrease in ddl concentration (Rainey et al. 2000) Effect not seen with enteric-coated ddl (Faragon and Pillero 2003; Friedland et al. 2002).Dextromethorphan
- Robitussin®, Vicks® Delsym®, Touro Dm® Cough Medicine
Increased levels /effects of dextromethorphan proposed (Levy et al. 2000).Interferon-alfa+ribavirin -
Rebetron® (possibly also pegylated interferon, Pegasys®) Antihepatitis C treatment Side effects can mimic opioid withdrawal symptoms and methadose is often increased (Schafer 2001; Sylvestre 2002).Nifedipine -
Procardia®, Adalat® Cardiac medication (Ca-channel blocker) Possible increase in nifedipine proposed (
Levy et al. 2000; Strang 1999)Stavudine (d4T)
-Zerit® NRTI antiretroviral Decrease in d4T concentration
; no effect on methadone
(Rainey et al. 2000).Zidovudine (AZT)
- Retrovir ®, AZT combinations, (Combivir®, Trizivir®) NRTI antiretoviral AZT concentration increased 40% with methadone
; more frequent AZT side effects are possible (McCance-Kantz et al. 1998).The opioids will be classified as: (1) Agonists (2) Antagonists (3) Mixed- Agonists - Antagonists.
|Opioids-Analgesics-Common 450 pathways with|
methadone; additive effects possible. Long-acting excitatory metabolites of meperidine and pro-poxyphene can reach toxic levels (Harrington
et al. 1999).
Warning: Use opioids with extreme care with alcohol, sedatives, anti-anxiety, and other medications and with your physician's supervision Dangerous when mixed!
- Alfenta® Hydrocodone
Duramorph®, MS Contin® Oxycodone -
AGAIN, TO READ THE COMPLETE ARTICLE THAT EXPLAINS HOW THESE MEDICATIONS INTERACT WITH METHADONE GO THE THE MAT of AMERICA, Inc. WEBSITE AT
Opioid Antagonists displaces methadone
causing severe withdrawal !!!!
Naltrexone - Revia® , Depade® Naloxone - Narcan®
Nalmefene - Revex®
The compounds that comprise the mixed agonist-antagonist group are more recent additions to the clinically important opioids. These drugs are semi-synthetic deriatives of morphine, the chemical structures of which have (1) agonistic activity at some k re-ceptors but antagonistic activity at µ receptors , e.g., pentazocine, butorphanol, and nalbuphine, or (2) partial agonistic activity at µ receptors and antagonistic activity at the k receptors, e.g., buprenorphine. All are effective analgesics since they stim-ulate either µ or k receptors.
Buprenorphine - Buprenex®, Subutex®, Suboxone® Butorphanol - Stadol®
Dezocine - Dalgan® Nalbuphine - Nubain® Pentazocine - Talwin®
The medications listed above as mixed-agonist-antagonist group can displace methadone on µ-opioid receptors to cause withdrawal (DeMaria 203; Kalvik et al. 1996)
Tramadol - Ultram® Synthetic Analgesic Potentially may cause withdrawal in persons already taking opioids (Ultram Pl 1998).
The drugs above may not be all inclusive of drugs/brands that might be contraindicated or interact with methadone