Drug: ConZip

ConZip™ (tramadol hydrochloride) capsules is a centrally acting synthetic analgesic in an extended-release oral formulation. The chemical name for tramadol hydrochloride is (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride. Its structural formula is: Figure 1
The molecular weight of tramadol hydrochloride is 299.8. It is a white, bitter, crystalline and odorless powder that is readily soluble in water and ethanol and has a pKa of 9.41. The n-octanol/water log partition coefficient (logP) is 1.35 at pH 7. ConZip™ capsules contain a total dose of tramadol HCl 100, 200 and 300 mg in a combination of immediate-release and extended-release components. Dosage Immediate-release Extended-release 100 mg 25 mg 75 mg 200 mg 50 mg 150 mg 300 mg 50 mg 250 mg ConZip™ capsules are white in color. Inactive ingredients include gelatin, titanium dioxide, shellac, FD & C Blue #2 aluminum lake (E132), D & C Red #7 calcium lake (E180), D & C Yellow #10 aluminum lake, lactose monohydrate 200 mesh, microcrystalline cellulose, povidone K30, corn starch, sodium starch glycolate, magnesium stearate, sucrose stearate, hypromellose, talc, polysorbate 80, Eudragit NE 30D, and simethicone emulsion. Last reviewed on RxList: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.

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The following serious or otherwise important adverse reactions are described in greater detail, in other sections:
  • Seizure risk [see WARNINGS AND PRECAUTIONS]
  • Suicide risk [see WARNINGS AND PRECAUTIONS]
  • Serotonin syndrome [see WARNINGS AND PRECAUTIONS]
  • Anaphylactoid and allergic reactions [see WARNINGS AND PRECAUTIONS]
  • Respiratory depression [see WARNINGS AND PRECAUTIONS]
  • Withdrawal symptoms [see WARNINGS AND PRECAUTIONS]
Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. ConZip™ capsules were administered to a total of 1987 patients in clinical trials. These included four double-blind and one long-term, open-label study in patients with osteoarthritis of the hip and knee. A total of 812 patients were 65 years or older. Adverse reactions with doses from 100 mg to 300 mg in the four pooled, randomized, doubleblind, placebo-controlled studies in patients with chronic non-malignant pain are presented in the following table (see Table 1). Table 1: Incidence (%) of patients with adverse reaction rates ≥ 5% from four doubleblind, placebo controlled studies in patients with moderate to moderately severe chronic pain by dose (N=1917).
Preferred Term CONZIP™ PLACEBO
(N=646)
n (%) 100 mg
(N=429)
n (%) 200 mg
(N=434)
n (%) 300 mg
(N=1054)
n (%) Headache 99 (23.1) 96 (22.1) 200 (19.0) 128 (19.8) Nausea 69 (16.1) 93 (21.4) 265 (25.1) 37 (5.7) Somnolence 50 (11.7) 60 (13.8) 170 (16.1) 26 (4.0) Dizziness 41 (9.6) 54 (12.4) 143 (13.6) 31 (4.8) Constipation 40 (9.3) 59 (13.6) 225 (21.3) 27 (4.2) Vomiting 28 (6.5) 45 (10.4) 98 (9.3) 12 (1.9) Arthralgia 23 (5.4) 20 (4.6) 53 (5.0) 33 (5.1) Dry Mouth 20 (4.7) 36 (8.3) 138 (13.1) 22 (3.4) Sweating 18 (4.2) 23 (5.3) 71 (6.7) 4 (0.6) Asthenia 15 (3.5) 26 (6.0) 91 (8.6) 17 (2.6) Pruritus 13 (3.0) 25 (5.8) 77 (7.3) 12 (1.9) Anorexia 9 (2.1) 23 (5.3) 60 (5.7) 1 (0.2) Insomnia 9 (2.1) 9 (2.1) 53 (5.0) 11 (1.7) The following adverse reactions were reported from all chronic pain studies (N=1917). The lists below include adverse reactions not otherwise noted in Table 1. Adverse reactions with incidence rates of 1.0% to < 5.0% Cardiac disorders: hypertension Gastrointestinal disorders: dyspepsia, flatulence General disorders: abdominal pain, accidental injury, chills, fever, flu syndrome, neck pain, pelvic pain Investigations: hyperglycemia, urine abnormality Metabolism and nutrition disorders: peripheral edema, weight loss Musculoskeletal, connective tissue and bone disorders: myalgia Nervous system disorders: paresthesia, tremor, withdrawal syndrome Psychiatric disorders: agitation, anxiety, apathy, confusion, depersonalization, depression, euphoria, nervousness Respiratory, thoracic and mediastinal disorders: bronchitis, pharyngitis, rhinitis, sinusitis Skin and subcutaneous tissue disorders: rash Urogenital disorders: prostatic disorder, urinary tract infection Vascular disorders: vasodilatation Adverse reactions with incidence rates of 0.5% to < 1.0% at any dose and serious adverse reactions reported in at least two patients. Cardiac disorders: EKG abnormal, hypotension, tachycardia Gastrointestinal disorders: gastroenteritis General disorders: neck rigidity, viral infection Hematologic/Lymphatic disorders: anemia, ecchymoses Metabolism and nutrition disorders: blood urea nitrogen increased, GGT increased, gout, SGPT increased Musculoskeletal disorders: arthritis, arthrosis, joint disorder, leg cramps Nervous system disorders: emotional lability, hyperkinesia, hypertonia, thinking abnormal, twitching, vertigo Respiratory disorders: pneumonia Skin and subcutaneous tissue disorders: hair disorder, skin disorder, urticaria Special Senses: eye disorder, lacrimation disorder Urogenital disorders: cystitis, dysuria, sexual function abnormality, urinary retention Read the ConZip (tramadol hydrochloride extended-release capsules) Side Effects Center for a complete guide to possible side effectsLearn More »

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General Dosing Considerations ConZip™ is an extended-release formulation intended for once a day dosing in adults aged 18 years and older. The tablets must be swallowed whole with liquid and must not be split, chewed, dissolved or crushed. Chewing, crushing or splitting the tablet could result in the uncontrolled delivery of tramadol, in overdose and death [see WARNINGS AND PRECAUTIONS, Drug Abuse And Dependence, and OVERDOSE]. Do not administer ConZip™ at a dose exceeding 300 mg per day. Do not use ConZip™ more than once daily or concomitantly with other tramadol products [see WARNINGS AND PRECAUTIONS]. Patients Not Currently on Tramadol Immediate-Release Products Initiate treatment with ConZip™ at a dose of 100 mg once daily and titrated up as necessary by 100 mg increments every five days to achieve a balance between relief of pain and tolerability. Patients Currently on Tramadol Immediate-Release Products Calculate the 24-hour tramadol IR dose and initiate a total daily dose of ConZip™ rounded down to the next lowest 100 mg increment. The dose may subsequently be individualized according to patient need. Due to limitations in flexibility of dose selection with ConZip™, some patients maintained on tramadol IR products may not be able to convert to ConZip™. Patients 65 Years of Age and Older Initiate dosing of an elderly patient (over 65 years of age) should be initiated cautiously, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. ConZip™ should be administered with even greater caution in patients over 75 years, due to the greater frequency of adverse events seen in this population. Patients with Renal Impairment The limited availability of dose strengths and once daily dosing of ConZip™ do not permit the dosing flexibility required for safe use in patients with severe renal impairment. Do not use ConZip™ in patients with creatinine clearance less than 30 mL/min [see Use In Specific Populations and CLINICAL PHARMACOLOGY]. Patients with Hepatic Impairment The limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release capsules do not permit the dosing flexibility required for safe use in patients with severe hepatic impairment. Do not use ConZip™ in patients with severe hepatic impairment (Child-Pugh Class C) [see Use In Specific Populations and CLINICAL PHARMACOLOGY]. Discontinuation of Treatment Withdrawal symptoms may occur if ConZip™ is discontinued abruptly. Clinical experience with tramadol suggests that withdrawal symptoms may be reduced by tapering ConZip™ [see WARNINGS AND PRECAUTIONS and Drug Abuse And Dependence]. Food Effects ConZip™ may be taken without regard to food [see CLINICAL PHARMACOLOGY].

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Drugs Affecting Seizure Threshold Concomitant use of tramadol increases the seizure risk in patients taking SSRI/SNRI antidepressants or anorectics, TCA antidepressants and other tricyclic compounds, other opioids, MAOIs, neuroleptics or other drugs that lower the seizure threshold [see WARNINGS AND PRECAUTIONS]. CYP2D6 and/or CYP3A4 inhibitors Tramadol is metabolized by CYP2D6 to form the active metabolite, O-desmethyl tramadol (M1). In vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine, paroxetine, and amitriptyline could result in some inhibition of the metabolism of tramadol. Tramadol is also metabolized by CYP3A4 [see CLINICAL PHARMACOLOGY]. Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin with ConZip™ may affect the metabolism of tramadol leading to altered tramadol exposure. Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors, such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors), and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome [see CLINICAL PHARMACOLOGY]. Serotonergic Drugs There have been post-marketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and α2-adrenergic blockers. Caution is advised when ConZip™ is co-administered with other drugs that may affect the serotonergic neurotransmitter systems, such as SSRIs, MAOIs, triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, or St. John's Wort. If concomitant treatment of ConZip™ with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see WARNINGS AND PRECAUTIONS]. Triptans Based on the mechanism of action of tramadol and the potential for serotonin syndrome, caution is advised when ConZip™ is co-administered with a triptan. If concomitant treatment of ConZip™ with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases [see WARNINGS AND PRECAUTIONS]. Interaction With Central Nervous System (CNS) Depressants ConZip™ should be used with caution and in reduced dosages when administered to patients receiving CNS depressants such as opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics. ConZip™ increases the risk of CNS and respiratory depression in these patients [see WARNINGS AND PRECAUTIONS]. Quinidine Quinidine is a strong inhibitor of CYP2D6. Coadministration of quinidine with an extended-release tramadol product resulted in a 50-60% increase in tramadol exposure and a 50-60% decrease in M1 exposure. The clinical consequences of these findings are unknown. [see CLINICAL PHARMACOLOGY]. In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism. Digoxin and Warfarins Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity and alteration of warfarin effect, including elevation of prothrombin times. CYP3A4 Inducers Administration of CYP3A4 inducers, such as carbamazepine, rifampin and St. John's Wort, with ConZip™ may affect the metabolism of tramadol leading to reduced tramadol exposure [see CLINICAL PHARMACOLOGY]. Patients taking carbamazepine, a CYP3A4 inducer, may have a significantly reduced analgesic effect of tramadol. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of ConZip™ and carbamazepine is not recommended. Drug Abuse And Dependence Controlled Substance ConZip™ is not a Controlled Substance. Abuse ConZip™ contains tramadol, a mu-agonist opioid. Tramadol, like other opioids used in analgesia, can be abused and is subject to criminal diversion. Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common. “Drug-seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. ConZip™, like other opioids, may be diverted for non-medical use. Careful record keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. ConZip™ is intended for oral use only. The crushed capsule poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol and other substances. With parenteral abuse, the capsule excipients can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Use in Drug and Alcohol Addiction ConZip™ is an opioid with no approved use for the management of addictive disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission is for the management of pain requiring opioid analgesia. Concerns about abuse and addiction should not prevent the proper management of pain. However all patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. 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. Withdrawal Symptoms 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. Generally, tolerance and/or withdrawal are more likely to occur the longer a patient is on continuous opioid therapy. Withdrawal symptoms may occur if ConZip™ is discontinued abruptly. Onset of adverse events are likely to occur after treatment is stopped. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Clinical experiences with tramadol suggests that withdrawal symptoms may be reduced by tapering ConZip™ when discontinuing tramadol therapy [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. Last reviewed on RxList: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

ConZip™ is indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time.

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ConZip™ is contraindicated in patients who have previously demonstrated hypersensitivity to tramadol, any other component of ConZip™, or opioids. Reactions range from pruritis to fatal anaphylactoid reactions [see WARNINGS AND PRECAUTIONS]. ConZip™ is contraindicated in patients with significant respiratory depression in unmonitored settings or the absence of resuscitative equipment. ConZip™ is contraindicated in patients with acute or severe bronchial asthma or hypercapnia in unmonitored settings or the absence of resuscitative equipment. Last reviewed on RxList: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Human Experience Acute overdosage with tramadol can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, and death. Deaths due to overdose have been reported with abuse and misuse of tramadol, by ingesting, inhaling, or injecting the crushed tablets. Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids. Management of Overdose In the treatment of tramadol overdosage, primary attention should be given to the reestablishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. While naloxone will reverse some, but not all, symptoms caused by overdosage with tramadol, the risk of seizures is also increased with naloxone administration. In animals, convulsions following the administration of toxic doses of ConZip™ could be suppressed with barbiturates or benzodiazepines but were increased with naloxone. Naloxone administration did not change the lethality of an overdose in mice. Hemodialysis is not expected to be helpful in an overdose because it removes less than 7% of the administered dose in a 4-hour dialysis period.

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Dosage Forms And Strengths ConZip™ is available in 100 mg, 200 mg and 300 mg extended-release capsules. 100 mg Capsules: White capsule imprinted with blue ink “G 252” on cap and “100” between lines on the body 200 mg Capsules: White capsule imprinted with violet ink “G 253” on cap and “200” between lines on the body 300 mg Capsules: White capsule imprinted with red ink “G 254” on cap and “300” between lines on the body Storage And Handling ConZip™ capsules (tramadol hydrochloride) are supplied as opaque white hard gelatin capsules, imprinted as follows. 100 mg Capsules: White Capsule imprinted with blue ink “G 252” on cap and “100” between lines on the body Bottle of 30 capsules: NDC 68025-053-30 200 mg Capsules: White capsule imprinted with violet ink “G 253” on cap and “200” between lines on the body Bottle of 30 capsules: NDC 68025-055-30 300 mg Capsules: White capsule imprinted with red ink “G 254” on cap and “300” between lines on the body Bottle of 30 capsules: NDC 68025-056-30 Storage Dispense in a tight container. Store at 25°C; excursions permitted to 15°C to 30°C (59°F to 86°F). Keep out of reach of children. Manufactured for: Vertical Pharmaceuticals, Inc., Sayreville, NJ 08872 USA. by: Galephar P R, Inc., Juncos, Puerto Rico 00777. Revised: June 2011 Last reviewed on RxList: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Seizure Risk Seizures have been reported in patients receiving tramadol within the recommended dosage range. Spontaneous post-marketing reports indicate that seizure risk is increased with doses of tramadol above the recommended range. Concomitant use of tramadol increases the seizure risk in patients taking: [see DRUG INTERACTIONS]
  • Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants or anorectics,
  • Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.),
  • Other opioids,
  • MAO inhibitors [see DRUG INTERACTIONS],
  • Neuroleptics, or
  • Other drugs that reduce the seizure threshold.
Risk of seizures may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). In tramadol overdose, naloxone administration may increase the risk of seizure. Suicide Risk
  • Do not prescribe ConZip™ for patients who are suicidal or addiction-prone. Consideration should be given to the use of non-narcotic analgesics in patients who are suicidal or depressed [see Drug Abuse And Dependence].
  • Prescribe ConZip™ with caution for patients with a history of misuse and/or are taking CNS-active drugs including tranquilizers or antidepressant drugs, or alcohol in excess, and patients who suffer from emotional disturbance or depression [see DRUG INTERACTIONS].
  • Tell your patients not to exceed the recommended dose and to limit their intake of alcohol [see DOSAGE AND ADMINISTRATION].
Serotonin Syndrome Risk The development of a potentially life-threatening serotonin syndrome may occur with use of tramadol products, including ConZip™, particularly with concomitant use of serotonergic drugs such as SSRIs, SNRIs, TCAs, MAOIs and triptans, with drugs which impair metabolism of serotonin (including MAOIs) and with drugs which impair metabolism of tramadol (CYP2D6 and CYP3A4 inhibitors). This may occur within the recommended dose. [see CLINICAL PHARMACOLOGY]. Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Anaphylactoid Reactions Serious and rarely fatal anaphylactoid reactions have been reported in patients receiving therapy with tramadol. When these events do occur it is often following the first dose. Other reported allergic reactions include pruritus, hives, bronchospasm, angioedema, toxic epidermal necrolysis and Stevens-Johnson syndrome. Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive ConZip™ [see CONTRAINDICATIONS]. Respiratory Depression Administer ConZip™ cautiously in patients at risk for respiratory depression. In these patients alternative non-opioid analgesics should be considered. If large doses of tramadol are administered with anesthetic medications or alcohol, respiratory depression may result. Respiratory depression should be treated as an overdose. If naloxone is to be administered, use cautiously because it may precipitate seizures [see OVERDOSAGE]. Interaction With Central Nervous System (CNS) Depressants, Including Alcohol and Drugs of Abuse Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. Use ConZip™ with caution and in reduced dosages when administered to patients receiving CNS depressants such as alcohol, opioids, anesthetic agents, narcotics, phenothiazines, tranquilizers or sedative hypnotics. ConZip™ increases the risk of CNS and respiratory depression in these patients. Alcohol-containing beverages should not be consumed by patients using ConZip™ [see DRUG INTERACTIONS, and OVERDOSAGE]. Patients with Increased Intracranial Pressure or Head Trauma Use ConZip™ with caution in patients with increased intracranial pressure or head injury. The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in these patients. Additionally, pupillary changes (miosis) from tramadol may obscure the existence, extent, or course of intracranial pathology. Clinicians should also maintain a high index of suspicion for adverse drug reaction when evaluating altered mental status in these patients if they are receiving ConZip™. Use in Ambulatory Patients ConZip™ may impair the mental and or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Caution patients initiating therapy with ConZip™ or those whose dose has been increased to refrain from potentially hazardous activities until it is established that their mental and physical abilities are not significantly impaired. Use With MAO Inhibitors and SSRIs Use ConZip™ with great caution in patients taking monoamine oxidase inhibitors. Animal studies have shown increased deaths with combined administration. Concomitant use of ConZip™ with MAO inhibitors or SSRI's increases the risk of adverse reactions, including seizure and serotonin syndrome. Withdrawal Symptoms Withdrawal symptoms may occur if ConZip™ is discontinued abruptly. These symptoms may include: anxiety, sweating, insomnia, rigors, pain, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, and rarely hallucinations. Clinical experience with other formulations of tramadol suggests that withdrawal symptoms may be reduced by tapering ConZip™ when discontinuing tramadol therapy. Misuse, Abuse and Diversion of Opioids ConZip™ contains tramadol, an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Tramadol can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing ConZip™ in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. ConZip™ could be abused by crushing, chewing, snorting, or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death [see Drug Abuse And Dependence, and OVERDOSAGE]. Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. The development of addiction to opioid analgesics in properly managed patients with pain has been reported to be rare. However, data are not available to establish the true incidence of addiction in chronic pain patients. Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product. Risk of Overdosage Serious potential consequences of overdosage with ConZip™ are central nervous system depression, respiratory depression and death. In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment [see OVERDOSAGE]. Acute Abdominal Conditions The administration of ConZip™ may complicate the clinical assessment of patients with acute abdominal conditions. Use In Specific Populations Pregnancy Teratogenic Effects - Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Use ConZip™ during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonatal seizures, neonatal withdrawal syndrome, fetal death and still birth have been reported during post-marketing reports with tramadol HCl immediate-release products. ConZip™ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Tramadol was not teratogenic at oral dose levels up to 50 mg/kg/day (1.6-fold the maximum daily human dose (MDHD)) in rats and 100 mg/kg (approximately 6.5-fold MDHD) in rabbits during organogenesis. However, embryo-fetal lethality, reductions in fetal weight and skeletal ossification, and increased supernumerary ribs were observed at a maternal toxic dose of 140 mg/kg in mice (approximately 2.3-fold MDHD), 80 mg/kg in rats (2.6-fold MDHD) or 300 mg/kg in rabbits (approximately 19-fold MDHD). Non-teratogenic Effects Tramadol caused a reduction in neonatal body weight at a dose of 50 mg/kg (1.6-fold the MDHD) and reduced pup survival at an oral dose of 80 mg/kg (approximately 2.6-fold MDHD) when rats were treated during late gestation throughout lactation period. Labor and Delivery ConZip™ should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks. Safe use in pregnancy has not been established. Chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn [see Drug Abuse And Dependence]. Tramadol has been shown to cross the placenta. The mean ratio of serum tramadol in the umbilical veins compared to maternal veins was 0.83 for 40 women given tramadol during labor. The effect of ConZip™, if any, on the later growth, development, and functional maturation of the child is unknown. Nursing Mothers ConZip™ is not recommended for obstetrical preoperative medication or for postdelivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post-dose was 100 μg of tramadol (0.1% of the maternal dose) and 27 μg of M1. It is not known whether this drug is excreted in human milk following an oral dose. Pediatric Use The safety and efficacy of ConZip™ in patients under 18 years of age have not been established. The use of ConZip™ in the pediatric population is not recommended. Geriatric Use In general, caution should be used when selecting the dose for an elderly patient. Usually, dose administration should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. Eight hundred and twelve elderly (65 years of age or older) subjects were exposed to ConZip™ in clinical trials. Of those subjects, two hundred and forty were 75 years of age and older. In general, higher incidence rates of adverse events were observed for patients older than 65 years of age compared with patients 65 years and younger, particularly for the following adverse events: nausea, constipation, somnolence, dizziness, dry mouth, vomiting, asthenia, pruritus, anorexia sweating, fatigue, weakness, postural hypotension and dyspepsia. For this reason, ConZip™ should be used with great caution in patients older than 75 years of age [see DOSAGE AND ADMINISTRATION]. Patients with Renal Impairment ConZip™ has not been studied in patients with renal impairment. Impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, M1. The limited availability of dose strengths of ConZip™ does not permit the dosing flexibility required for safe use in patients with severe renal impairment. Therefore, ConZip™ should not be used in patients with severe renal impairment [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]. Patients with Hepatic Impairment ConZip™ has not been studied in patients with hepatic impairment. The limited availability of dose strengths of ConZip™ does not permit the dosing flexibility required for safe use in patients with severe hepatic impairment. Therefore, ConZip™ should not be used in patients with severe hepatic impairment [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

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