Heptadone - General Information
A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Heptadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)
Pharmacology of Heptadone
Heptadone is a synthetic opioid analgesic with multiple actions quantitatively similar to those at morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, Heptadone is more active and more toxic than morphine. Heptadone is indicated for relief of severe pain, for detoxification treatment of narcotic addiction, and for temporary maintenance treatment of narcotic addiction. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The Heptadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.
Heptadone for patients
DOLOPHINE® HYDROCHLORIDE CII
(Methadone Hydrochloride Tablets), 5 mg and 10 mg
Keep DOLOPHINE out of the reach of children. Accidental overdose by a child is a medical emergency and can result in death. If a child accidentally takes DOLOPHINE, get emergency help right away.
Do not take a higher dose of DOLOPHINE or take it more often than prescribed. This can lead to an overdose and possible death.
Read the Patient Information that comes with DOLOPHINE before you take it and each time you get a new prescription. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment. Share the important information in this leaflet with members of your household.
What Is The Most Important Information I Should Know About DOLOPHINE?
- DOLOPHINE can cause life threatening breathing problems which can
lead to death. These problems are more likely to happen when DOLOPHINE is
first started or in someone who is not already taking other narcotic (opioid)
- Breathing problems from DOLOPHINE may not happen right away after taking a dose. Sometimes breathing problems will happen a while after you take a dose, even after pain has returned. It is very important that you take DOLOPHINE exactly as your doctor has prescribed. Talk to your doctor about your pain. Your doctor can decide if your DOLOPHINE dose needs to be changed.
- DOLOPHINE can cause life-threatening heart beat problems that can lead to death. Most heart beat problems have happened in people using large doses of DOLOPHINE for pain treatment. Some heart beat problems have happened in people using smaller doses of DOLOPHINE for treatment of narcotic drug addiction.
What is DOLOPHINE?
DOLOPHINE is a prescription medicine that contains methadone, which is a narcotic pain medicine similar to morphine. DOLOPHINE is a federally controlled substance (CII) because it is a strong opioid pain medicine that can be abused by people who abuse prescription medicines or street drugs.
- Prevent theft and misuse. Keep your DOLOPHINE tablets in a safe place to protect them from theft. Never give DOLOPHINE to anyone else even if they have the same symptoms you have. It may harm them and even cause death. Selling or giving away this medicine is dangerous and against the law.
DOLOPHINE is used:
- to treat moderate to severe pain in people that do not respond to non-narcotic pain medicines;
- to control withdrawal symptoms in patients being treated for narcotic drug addiction;
- for maintenance treatment of narcotic drug addiction along with other social and medical services. Stopping maintenance treatment of narcotic drug addiction with DOLOPHINE may result in a return to narcotic drug use.
Who Should Not Take DOLOPHINE?
Do not take DOLOPHINE if you:
- have severe asthma or severe lung problems.
- have a blockage or obstruction in your intestines.
- are allergic to methadone or anything else in DOLOPHINE. See the end of this leaflet for a complete list of ingredients.
What Should I Tell my Doctor Before I Start Taking DOLOPHINE?
DOLOPHINE may not be right for you. Before starting DOLOPHINE, tell your doctor about all your medical and mental conditions including a history of drug or alcohol abuse or addiction.
Tell your doctor if you:
- are pregnant or plan to become pregnant. DOLOPHINE may harm your unborn baby.
- are breast feeding. DOLOPHINE passes through your breast milk and may harm your baby. You should choose to use DOLOPHINE or breastfeed, but not both.
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicines may cause serious or life-threatening medical problems when taken with DOLOPHINE. Be especially careful about other medicines that may make you sleepy, such as other pain medicines, anti-depressant medicines, sleeping pills, anxiety medicines, antihistamines, or tranquilizers. Sometimes, the doses of certain medicines (including DOLOPHINE) may need to be changed if they are used together.
Do not take any medicine while using DOLOPHINE until you have first talked to your doctor or pharmacist. They will be able to tell you if it is safe to take other medicines while you are using DOLOPHINE.
Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist each time you get a new medicine.
How Should I Take DOLOPHINE?
- Take DOLOPHINE exactly as prescribed. Follow your doctor's directions exactly. Your doctor may change your dose based on your reactions to the medicine. Do not change your dose unless your doctor tells you to change it. Do not take a higher dose of DOLOPHINE or take it more often than prescribed. This can lead to an overdose and possibly death.
- If you take too much DOLOPHINE or overdose, call 911 or your local emergency number right away.
- Review your medical conditions regularly with your doctor to determine if you still need DOLOPHINE, or if the dose needs to be adjusted.
- When starting treatment with DOLOPHINE for narcotic drug dependence, you should be aware that your dose of methadone will "hold" for longer periods of time as treatment goes on.
- Stopping DOLOPHINE. Ask your doctor for instructions on how to stop this medicine slowly to avoid uncomfortable symptoms. You should not stop taking DOLOPHINE all at once if you have been taking it for more than a few days.
- Tell all health professionals that treat you that you take DOLOPHINE.
- After stopping treatment with DOLOPHINE, flush the unused tablets down the toilet.
What Should I Avoid While Taking DOLOPHINE?
- Do not drive, operate heavy machinery, or do other possible dangerous activities until you know how DOLOPHINE affects you. DOLOPHINE can make you sleepy. Ask your doctor when it is okay to do these activities.
- Do not drink alcohol while using DOLOPHINE. It may increase the chance of having dangerous side effects.
- Do not take other medicines with DOLOPHINE without first talking with your doctor.
What are the Possible Side Effects of DOLOPHINE?
- DOLOPHINE can cause life threatening breathing and heart problems which
can lead to death See "What Is The Most Important Information I Should
Know About DOLOPHINE?"
- Call your doctor or get medical help right away if you:
- have trouble breathing
- have extreme drowsiness and breathing slows down
- have slow shallow breathing (little chest movement with breathing)
- fast or slowed heartbeat
- feel faint, very dizzy, confused, have palpitations (irregular heart beat) or any other unusual symptoms
- Call your doctor or get medical help right away if you:
These can be symptoms that you have taken too much (overdose of) DOLOPHINE,
or the dose is too high for you. They can also be symptoms of a serious heart
These symptoms can lead to serious problems or death if not treated right away.
- DOLOPHINE can cause your blood pressure to drop. This can make you feel dizzy if you get up too fast from sitting or lying down.
- DOLOPHINE can cause physical dependence. Do not stop taking DOLOPHINE or any other opioid without first talking to your doctor. You could become sick with uncomfortable withdrawal symptoms because your body has become used to these medicines. Talk to your doctor about slowly stopping DOLOPHINE to avoid getting sick with withdrawal symptoms. Physical dependency is not the same as drug addiction.
- For patients using DOLOPHINE for pain treatment, there is a chance of abuse or addiction with DOLOPHINE. The chance is higher if you are or have been addicted to or abused other medicines, street drugs, or alcohol, or if you have a history of mental problems.
Talk to your doctor about any side effects that bother you or that do not go away.
These are not all the possible side effects of DOLOPHINE. For a complete list, ask your doctor or pharmacist.
How Should I Store DOLOPHINE Tablets?
- Keep DOLOPHINE in a safe place away from children. Accidental use by a child is a medical emergency that can result in death. If a child accidentally takes DOLOPHINE, get emergency help right away.
- Keep DOLOPHINE at room temperature, 59 to 86°F (15 to 30°C).
- Always keep DOLOPHINE in a secure place to protect from theft.
- Dispose of any unused DOLOPHINE remaining from a prescription as soon as they are no longer needed. Unused tablets should be flushed down the toilet.
General Information About DOLOPHINE.
Medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use DOLOPHINE for a condition for which it was not prescribed. Do not give DOLOPHINE to other people, even if they have the same symptoms you have. DOLOPHINE can harm other people and even cause death. Sharing DOLOPHINE is against the law.
This leaflet summarizes the most important information about DOLOPHINE. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about DOLOPHINE that is written for healthcare professionals, or you can visit www.Roxane.com or call 1-800-962-8364.
What are the Ingredients in DOLOPHINE?
Active Ingredient: methadone hydrochloride, USP
Inactive Ingredients: magnesium stearate, microcrystalline cellulose, and starch.
In vitro results suggest that methadone undergoes hepatic N-demethylation by cytochrome P450 enzymes, principally CYP3A4, CYP2B6, CYP2C19 and to a lesser extent by CYP2C9 and CYP2D6. Coadministration of methadone with CYP inducers of these enzymes may result in a more rapid metabolism and potential for decreased effects of methadone, whereas administration with CYP inhibitors may reduce metabolism and potentiate methadone's effects. Although antiretroviral drugs such as efavirenz, nelfinavir, nevirapine, ritonavir, lopinavir+ritonavir combination are known to inhibit CYPs, they are shown to reduce the plasma levels of methadone, possibly due to their CYP induction activity. Therefore, drugs administered concomitantly with methadone should be evaluated for interaction potential; clinicians are advised to evaluate individual response to drug therapy.
Opioid Antagonists, Mixed Agonist/Antagonists, and Partial Agonists
As with other mu-agonists, patients maintained on methadone may experience withdrawal symptoms when given opioid antagonists, mixed agonist/antagonists, and partial agonists. Examples of such agents are naloxone, naltrexone, pentazocine, nalbuphine, butorphanol, and buprenorphine.
Abacavir, amprenavir, efavirenz, nelfinavir, nevirapine, ritonavir, lopinavir+ritonavir combination - Coadministration of these anti-retroviral agents resulted in increased clearance or decreased plasma levels of methadone. Methadone-maintained patients beginning treatment with these antiretroviral drugs should be monitored for evidence of withdrawal effects and methadone dose should be adjusted accordingly.
Didanosine and Stavudine - Experimental evidence demonstrated that methadone decreased the AUC and peak levels for didanosine and stavudine, with a more significant decrease for didanosine. Methadone disposition was not substantially altered.
Zidovudine - Experimental evidence demonstrated that methadone increased the area under the concentration-time curve (AUC) of zidovudine which could result in toxic effects.
Cytochrome P450 Inducers
Methadone-maintained patients beginning treatment with CYP3A4 inducers should be monitored for evidence of withdrawal effects and methadone dose should be adjusted accordingly. The following drug interactions were reported following coadministration of methadone with inducers of cytochrome P450 enzymes:
Rifampin - In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms.
Phenytoin - In a pharmacokinetic study with patients on methadone maintenance therapy, phenytoin administration (250 mg b.i.d. initially for 1 day followed by 300 mg QD for 3 to 4 days) resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. Upon discontinuation of phenytoin, the incidence of withdrawal symptoms decreased and methadone exposure increased to a level comparable to that prior to phenytoin administration.
St. John's Wort, Phenobarbital, Carbamazepine
Administration of methadone along with other CYP3A4 inducers may result in withdrawal symptoms.
Cytochrome P450 Inhibitors
Since the metabolism of methadone is mediated primarily by CYP3A4 isozyme, coadministration of drugs that inhibit CYP3A4 activity may cause decreased clearance of methadone. The expected clinical results would be increased or prolonged opioid effects. Thus, methadone-treated patients coadministered strong inhibitors of CYP3A4, such as azole antifungal agents (e.g., ketoconazole) and macrolide antibiotics (e.g., erythromycin), with methadone should be carefully monitored and dosage adjustment should be undertaken if warranted. Some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) may increase methadone plasma levels upon coadministration with methadone and result in increased opiate effects and/or toxicity.
Voriconazole - Repeat dose administration of oral voriconazole (400mg Q12h for 1 day, then 200mg Q12h for 4 days) increased the Cmax and AUC of (R)-methadone by 31% and 47%, respectively, in subjects receiving a methadone maintenance dose (30 to 100 mg QD). The Cmax and AUC of (S)-methadone increased by 65% and 103%, respectively. Increased plasma concentrations of methadone have been associated with toxicity including QT prolongation. Frequent monitoring for adverse events and toxicity related to methadone is recommended during coadministration. Dose reduction of methadone may be needed.
Monoamine Oxidase (MAO) Inhibitors - Therapeutic doses of meperidine have precipitated severe reactions in patients concurrently receiving monoamine oxidase inhibitors or those who have received such agents within 14 days. Similar reactions thus far have not been reported with methadone. However, if the use of methadone is necessary in such patients, a sensitivity test should be performed in which repeated small, incremental doses of methadone are administered over the course of several hours while the patient's condition and vital signs are under careful observation.
Desipramine - Blood levels of desipramine have increased with concurrent methadone administration.
Potentially Arrhythmogenic Agents
Extreme caution is necessary when any drug known to have the potential to prolong the QT interval is prescribed in conjunction with methadone. Pharmacodynamic interactions may occur with concomitant use of methadone and potentially arrhythmogenic agents such as class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers.
Caution should also be exercised when prescribing methadone concomitantly with drugs capable of inducing electrolyte disturbances (hypomagnesemia, hypokalemia) that may prolong the QT interval. These drugs include diuretics, laxatives, and, in rare cases, mineralocorticoid hormones.
Interactions with Alcohol and Drugs of Abuse
Methadone may be expected to have additive effects when used in conjunction with alcohol, other opioids or CNS depressants, or with illicit drugs that cause central nervous system depression. Deaths have been reported when methadone has been abused in conjunction with benzodiazepines.
Anxiety - Since methadone as used by tolerant patients at a constant maintenance dosage does not act as a tranquilizer, patients who are maintained on this drug will react to life problems and stresses with the same symptoms of anxiety as do other individuals. The physician should not confuse such symptoms with those of narcotic abstinence and should not attempt to treat anxiety by increasing the dose of methadone. The action of methadone in maintenance treatment is limited to the control of narcotic withdrawal symptoms and is ineffective for relief of general anxiety.
Acute Pain - Maintenance patients on a stable dose of methadone who experience physical trauma, postoperative pain or other acute pain cannot be expected to derive analgesia from their existing dose of methadone. Such patients should be administered analgesics, including opioids, in doses that would otherwise be indicated for non-methadone-treated patients with similar painful conditions. Due to the opioid tolerance induced by methadone, when opioids are required for management of acute pain in methadone patients, somewhat higher and/or more frequent doses will often be required than would be the case for non-tolerant patients.
Risk of Relapse in Patients on Methadone Maintenance Treatment of Opioid Addiction
Abrupt opioid discontinuation can lead to development of opioid withdrawal symptoms. Presentation of these symptoms have been associated with an increased risk of susceptible patients to relapse to illicit drug use and should be considered when assessing the risks and benefit of methadone use.
Tolerance and Physical Dependence
Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and/or tolerance are not unusual during chronic opioid therapy.
If methadone is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur. The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
In general, chronically administered methadone should not be abruptly discontinued.
Methadone should be given with caution and the initial dose reduced in certain patients, such as the elderly and debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture. The usual precautions appropriate to the use of parenteral opioids should be observed and the possibility of respiratory depression should always be kept in mind.
Methadone is contraindicated in patients with a known hypersensitivity to methadone hydrochloride or any other ingredient in DOLOPHINE.
Methadone is contraindicated in any situation where opioids are contraindicated such as: patients with respiratory depression (in the absence of resuscitative equipment or in unmonitored settings), and in patients with acute bronchial asthma or hypercarbia.
Methadone is contraindicated in any patient who has or is suspected of having a paralytic ileus.
Additional information about Heptadone
Heptadone Indication: For the treatment of dry cough, drug withdrawal syndrome, opioid type drug dependence, and pain.
Mechanism Of Action: Heptadone is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone's efficacy is unknown. Other NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.
Drug Interactions: Amobarbital The barbiturate decreases the effect of methadone
Aprobarbital The barbiturate decreases the effect of methadone
Butabarbital The barbiturate decreases the effect of methadone
Butalbital The barbiturate decreases the effect of methadone
Butethal The barbiturate decreases the effect of methadone
Carbamazepine Carbamazepine decreases levels of methadone
Cimetidine Cimetidine increases the effect of the narcotic
Dihydroquinidine barbiturate The barbiturate decreases the effect of methadone
Fluvoxamine Fluvoxamine increases the effect and toxicity of methadone
Heptabarbital The barbiturate decreases the effect of methadone
Methohexital The barbiturate decreases the effect of methadone
Hexobarbital The barbiturate decreases the effect of methadone
Methylphenobarbital The barbiturate decreases the effect of methadone
Naltrexone Naltrexone may precipitate a withdrawal syndrome in opioid-dependent individuals
Pentobarbital The barbiturate decreases the effect of methadone
Phenobarbital The barbiturate decreases the effect of methadone
Nelfinavir Nelfinavir decreases the effect of methadone
Primidone The barbiturate decreases the effect of methadone
Quinidine barbiturate The barbiturate decreases the effect of methadone
Secobarbital The barbiturate decreases the effect of methadone
Talbutal The barbiturate decreases the effect of methadone
St. John's Wort St. John's Wort decreases levels/effect of methadone
Zidovudine Heptadone increases the effect and toxicity of zidovudine
Ritonavir The protease inhibitor decreases the effect of methadone
Amprenavir The protease inhibitor decreases the effect of methadone
Fosamprenavir The protease inhibitor decreases the effect of methadone
Efavirenz The antiretroviral agent decreases the effect of methadone
Nevirapine The antiretroviral agent decreases the effect of methadone
Ethotoin The hydantoin decreases the effect of methadone
Fosphenytoin The hydantoin decreases the effect of methadone
Mephenytoin The hydantoin decreases the effect of methadone
Phenytoin The hydantoin decreases the effect of methadone
Rifabutin The rifamycin decreases the effect of methadone
Rifampin The rifamycin decreases the effect of methadone
Rifapentine The rifamycin decreases the effect of methadone
Food Interactions: Not Available
Generic Name: Methadone
Synonyms: (+/-)-Methadone; (+/-)-Methadone hydrochloride; DL-Methadone hydrochloride; dl-Methadone; Methadone HCL; Methadone hydrochloride; Methadon; Phenadone hydrochloride
Drug Category: Narcotics; Antitussives; Analgesics; Opiate Agonists
Drug Type: Small Molecule; Approved
Absorption: Well absorbed following oral administration. The bioavailability of methadone ranges between 36 to 100%.
Toxicity (Overdose): In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.
Protein Binding: In plasma, methadone is predominantly bound to α1-acid glycoprotein (85% to 90%).
Biotransformation: Hepatic. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine.
Half Life: 24-36 hours
Dosage Forms of Heptadone: Tablet Oral
Chemical IUPAC Name: 6-dimethylamino-4,4-di(phenyl)heptan-3-one
Chemical Formula: C21H27NO
Methadone on Wikipedia: https://en.wikipedia.org/wiki/Methadone
Organisms Affected: Humans and other mammals