Australia - English - Department of Health (Therapeutic Goods Administration)

glaxosmithkline australia pty ltd - hpv type 16 l1 protein, quantity: 20 microgram; hpv type 18 l1 protein, quantity: 20 microgram - injection, suspension - excipient ingredients: monobasic sodium phosphate; aluminium hydroxide hydrate; water for injections; 3-o-desacyl-4'-monophosphoryl lipid a; sodium chloride - cervarix is indicated in females from 10 to 45 years of age for the prevention of persistent infection, premalignant cervical lesions and cervical cancer caused by human papillomavirus types 16 and 18. lmmunogenicity studies have been conducted in females aged 10 to 14 years and 26 to 45 years to link efficacy in females aged 15 to 25 years to other populations (see precautions and clinical trials).

Australia - English - Department of Health (Therapeutic Goods Administration)

merck sharp & dohme (australia) pty ltd - hpv type 6 l1 protein, quantity: 20 microgram; hpv type 11 l1 protein, quantity: 40 microgram; hpv type 16 l1 protein, quantity: 40 microgram; hpv type 18 l1 protein, quantity: 20 microgram - injection, suspension - excipient ingredients: aluminium; histidine; polysorbate 80; borax; water for injections; sodium chloride - gardasil is indicated in females aged 9 through 45 years* for the prevention of cervical, vulvar, vaginal and anal cancer, precancerous or dysplastic lesions, genital warts, and infection caused by human papillomavirus (hpv) types 6, 11, 16, and 18 (which are included in the vaccine). gardasil is indicated in males 9 through 26 years of age for the prevention of anal cancer, precancerous or dysplastic lesions, external genital lesions and infection caused by hpv types 6, 11, 16, and 18 (which are included in the vaccine). *immunogenicity studies have been conducted to link efficacy in females and males aged 16 to 26 years to the younger populations.

New Zealand - English - Medsafe (Medicines Safety Authority)

novartis new zealand ltd - aldesleukin 18 miu (interleukin-2 (recombinant human));   - powder for injection - 18 miu - active: aldesleukin 18 miu (interleukin-2 (recombinant human))   excipient: dibasic sodium phosphate dihydrate mannitol monobasic sodium phosphate dihydrate sodium laurilsulfate - proleukin is indicated for the treatment of metastatic renal cell carcinoma (mrcc).

Singapore - English - HSA (Health Sciences Authority)

link healthcare singapore pte ltd - aldesleukin - injection, powder, for solution - 18 miu/vial - aldesleukin 18 miu/vial

United States - English - NLM (National Library of Medicine)

ventura corporation ltd - avobenzone (unii: g63qqf2nox) (avobenzone - unii:g63qqf2nox), octisalate (unii: 4x49y0596w) (octisalate - unii:4x49y0596w), zinc oxide (unii: soi2loh54z) (zinc oxide - unii:soi2loh54z), octinoxate (unii: 4y5p7mud51) (octinoxate - unii:4y5p7mud51), oxybenzone (unii: 95oos7ve0y) (oxybenzone - unii:95oos7ve0y) - avobenzone 0.0003 g in 1 g

United States - English - NLM (National Library of Medicine)

blue earth diagnostics - fluciclovine f-18 (unii: 38r1q0l1ze) (fluciclovine f-18 - unii:38r1q0l1ze) - fluciclovine f-18 221 mci in 1 ml - axumin is indicated for positron emission tomography (pet) in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (psa) levels following prior treatment. none risk summary axumin is not indicated for use in females and there is no information on the risk of adverse development outcomes in pregnant women or animals with the use of fluciclovine f 18. risk summary axumin is not indicated for use in females and there is no information of the presence of fluciclovine f 18 in human milk. safety and effectiveness have not been established in pediatric patients. of the total number of patients in clinical studies of axumin, the average age was 66 years with a range of 21 to 90 years. no overall differences in safety or effectiveness were observed between older subjects and younger subjects.

United States - English - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j) - tramadol hydrochloride 100 mg - tramadol hydrochloride extended-release tablets are indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. limitations of use - because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosages or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations [see warnings and precautions (5.1)] , reserve tramadol hydrochloride extended-release tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. - tramadol hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic. tramadol hydrochloride extended-release tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions (5.6)] - post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions (5.6)] . tramadol hydrochloride extended-release tablets are also contraindicated in patients with: - significant respiratory depression [see warnings and precautions (5.2)] - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions (5.12)] - known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions (5.16)] - hypersensitivity to tramadol (e.g., anaphylaxis) [see warnings and precautions (5.17), adverse reactions (6.2)] - concurrent use of monoamine oxidase inhibitors (maois) or use within the last 14 days [see drug interactions (7)] . risk summary use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions (5.4)] . available data with tramadol hydrochloride extended-release tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, tramadol administration during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd). tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the mrhd [see data]. based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions (5.4)] . neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol during post-approval use of tramadol immediate-release products. labor or delivery opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. tramadol hydrochloride extended-release tablets are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. opioid analgesics, including tramadol hydrochloride extended-release tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. 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 tramadol hydrochloride extended-release tablets, if any, on the later growth, development, and functional maturation of the child is unknown. data animal data tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. these doses on a mg/m2 basis are 1.9, 0.8, and 4.9 times the maximum recommended human daily dosage (mrhd) for mouse, rat and rabbit, respectively. no drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. embryo and fetal toxicity consisted primarily of decreased fetal weights, decreased skeletal ossification, and increased supernumerary ribs at maternally toxic dose levels. transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. the dosages listed for mouse, rat, and rabbit are 2.3, 2.6, and 19 times the mrhd, respectively. tramadol was evaluated in pre- and post-natal studies in rats. progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (1.6 times the mrhd) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (2.6 times the mrhd). risk summary tramadol hydrochloride extended-release tablets are not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. tramadol and its metabolite, o-desmethyl tramadol (m1), are present in human milk. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the m1 metabolite is more potent than tramadol in mu opioid receptor binding [see clinical pharmacology (12.1) ]. published studies have reported tramadol and m1 in colostrum with administration of tramadol to nursing mothers in the early post-partum period. women who are ultra-rapid metabolizers of tramadol may have higher than expected serum levels of m1, potentially leading to higher levels of m1 in breast milk that can be dangerous in their breastfed infants. in women with normal tramadol metabolism, the amount of tramadol secreted into human milk is low and dose-dependent. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with tramadol hydrochloride extended-release tablets. clinical considerations if infants are exposed to tramadol hydrochloride extended-release tablets through breast milk, they should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. data  following a single iv 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of m1. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions (6.2), clinical pharmacology (12.2), nonclinical toxicology (13.1) ]. the safety and effectiveness of tramadol hydrochloride extended-release tablets in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received tramadol [see warnings and precautions (5.6)] . in some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome p450 isoenzyme 2d6). children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. because of the risk of life-threatening respiratory depression and death: - tramadol hydrochloride extended-release tablets are contraindicated for all children younger than age 12 years of age [see contraindications (4) ]. - tramadol hydrochloride extended-release tablets are contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy [see  contraindications (4) ]. - avoid the use of tramadol hydrochloride extended-release tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. [see warnings and precautions (5.6)] . nine-hundred-one elderly (65 years of age or older) subjects were exposed to tramadol hydrochloride extended-release tablets in clinical trials. of those subjects, 156 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: constipation, fatigue, weakness, postural hypotension and dyspepsia. for this reason, tramadol hydrochloride extended-release tablets should be used with caution in patients over 65 years of age, and with even greater caution in patients older than 75 years of age [see dosage and administration (2.5), clinical pharmacology (12.3)]. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioidtolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of tramadol hydrochloride extended-release tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see warnings and precautions (5.12)] . tramadol is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. metabolism of tramadol and m1 is reduced in patients with advanced cirrhosis of the liver. tramadol hydrochloride extended-release tablets have not been studied in patients with severe hepatic impairment. the limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release tablets do not permit the dosing flexibility required for safe use in patients with severe hepatic impairment (child-pugh class c). therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe hepatic impairment [see clinical pharmacology (12.3) ]. impaired renal function results in a decreased rate and extent of excretion of tramadol and its active metabolite, m1. tramadol hydrochloride extended-release tablets have not been studied in patients with severe renal impairment (clcr < 30 ml/min). the limited availability of dose strengths and once daily dosing of tramadol hydrochloride extended-release tablets do not permit the dosing flexibility required for safe use in patients with severe renal impairment (child-pugh class c). therefore, tramadol hydrochloride extended-release tablets should not be used in patients with severe renal impairment [see clinical pharmacology (12.3)] . tramadol hydrochloride extended-release tablet contains tramadol, a scheduled iv controlled substance. tramadol hydrochloride extended-release tablets contain tramadol, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see warnings and precautions (5.1)] . misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of tramadol hydrochloride extended-release tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of tramadol hydrochloride extended-release tablets with alcohol and other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of tramadol hydrochloride extended-release tablets abuse include those with a history of prolonged use of any opioid, including products containing tramadol, those with a history of drug or alcohol abuse, or those who use tramadol hydrochloride extended-release tablets in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. 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 healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. tramadol hydrochloride extended-release tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of tramadol hydrochloride extended-release tablets abuse of tramadol hydrochloride extended-release tablets poses a risk of overdose and death. this is increased with concurrent use of tramadol hydrochloride extended-release tablets with alcohol and/or other cns depressants. tramadol hydrochloride extended-release tablets is approved for oral use only. inappropriate intravenous, intramuscular, or subcutaneous use of tramadol hydrochloride extended-release tablets can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. with parenteral abuse the inactive ingredients can result in local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue tramadol hydrochloride extended-release tablets in a patient physically dependent on opioids. rapid tapering of tramadol hydrochloride extended-release tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing tramadol hydrochloride extended-release tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride extended-release tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see dosage and administration (2.5), and warnings and precautions (5.18)] . infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see use in specific populations (8.1 )].

United States - English - NLM (National Library of Medicine)

global isotopes, llc d/b/a zevacor molecular - fludeoxyglucose f-18 (unii: 0z5b2cjx4d) (fludeoxyglucose f-18 - unii:0z5b2cjx4d) - fludeoxyglucose f-18 20 mci in 1 ml - fludeoxyglucose f18 injection, usp is indicated for positron emission tomography (pet) imaging in the following settings: for assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormality found by other testing modalities, or in patients with an existing diagnosis of cancer.  for the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.  for the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures. none. ( 4) pregnancy category c animal reproduction studies have not been conducted with fludeoxyglucose f18 injection. it is also not known whether fludeoxyglucose f18 injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.  consider alternative diagnostic te

United States - English - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - tramadol hydrochloride (unii: 9n7r477wck) (tramadol - unii:39j1lgj30j), acetaminophen (unii: 362o9itl9d) (acetaminophen - unii:362o9itl9d) - tramadol hydrochloride 37.5 mg - tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. limitations of use tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see warnings and precautions ( 5.1)] , reserve tramadol hydrochloride and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]: - have not been tolerated, or are not expected to be tolerated, - have not provided adequate analgesia, or are not expected to provide adequate analgesia. tramadol hydrochloride and acetaminophen tablets should not be used for an extended period of time. tramadol hydrochloride and acetaminophen tablets are contraindicated for: - all children younger than 12 years of age [see warnings and precautions ( 5.6)]. - post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see warnings and precautions ( 5.6)]. tramadol hydrochloride and acetaminophen tablets are also contraindicated in patients with: - significant respiratory depression [see warnings and precautions ( 5.2)] . - acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see warnings and precautions ( 5.13)] . - patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see warnings and precautions ( 5.18)] . - previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see warnings and precautions ( 5.19)] . - concurrent use of monoamine oxidase inhibitors (maois) or use within the last 14 days [see drug interactions ( 7)]. use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see warnings and precautions ( 5.4)] . available data with tramadol hydrochloride and acetaminophen tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. in animal reproduction studies, the combination of tramadol and acetaminophen decreased fetal weights and increased supernumerary ribs at 1.6 times the maximum recommended human daily dosage (mrhd). in separate animal reproduction studies, tramadol administration alone during organogenesis decreased fetal weights and reduced ossification in mice, rats, and rabbits at 1.4, 0.6, and 3.6 times the maximum recommended human daily dosage (mrhd). tramadol decreased pup body weight and increased pup mortality at 1.2 and 1.9 times the mrhd. reproductive and developmental studies in rats and mice from the published literature identified adverse events at clinically relevant doses with acetaminophen. treatment of pregnant rats with doses of acetaminophen approximately 1.3 times the maximum human daily dose (mrhd) showed evidence of fetotoxicity and increases in bone variations in the fetuses. in another study, necrosis was observed in the liver and kidney of both pregnant rats and fetuses at doses approximately 1.9 times the mhdd. in mice treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproduction were seen in a continuous breeding study. a reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation [see data] . based on animal data, advise pregnant women of the potential risk to a fetus. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. fetal/neonatal adverse reactions use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in respiratory depression and physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly [see warnings and precautions ( 5.4)] . neonatal seizures, neonatal withdrawal syndrome, fetal death and stillbirth have been reported with tramadol hydrochloride during postmarketing. labor or delivery tramadol hydrochloride and acetaminophen tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in the neonate. tramadol hydrochloride and acetaminophen tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including tramadol hydrochloride and acetaminophen tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. 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 tramadol hydrochloride and acetaminophen tablets, if any, on the later growth, development, and functional maturation of the child is unknown. animal data no drug-related teratogenic effects were observed in the progeny of rats treated orally with tramadol and acetaminophen. the tramadol/acetaminophen combination product was shown to be embryotoxic and fetotoxic in rats at a maternally toxic dose, 50/434 mg/kg tramadol/acetaminophen (1.6 times the maximum daily human tramadol/acetaminophen dosage), but was not teratogenic at this dose level. embryo and fetal toxicity consisted of decreased fetal weights and increased supernumerary ribs. tramadol has been shown to be embryotoxic and fetotoxic in mice, (120 mg/kg), rats (25 mg/kg) and rabbits (75 mg/kg) at maternally toxic dosages, but was not teratogenic at these dose levels. these doses on a mg/m 2 basis are 1.9, 0.8, and 4.9 times the maximum recommended human daily dosage (mrhd) for mouse, rat and rabbit, respectively. no drug-related teratogenic effects were observed in progeny of mice (up to 140 mg/kg), rats (up to 80 mg/kg) or rabbits (up to 300 mg/kg) treated with tramadol by various routes. embryo and fetal toxicity consisted primarily of decreased fetal weights, skeletal ossification and increased supernumerary ribs at maternally toxic dose levels. transient delays in developmental or behavioral parameters were also seen in pups from rat dams allowed to deliver. embryo and fetal lethality were reported only in one rabbit study at 300 mg/kg, a dose that would cause extreme maternal toxicity in the rabbit. the dosages listed for mouse, rat and rabbit are 2.3, 2.6, and 19 times the mrhd, respectively. tramadol alone was evaluated in peri- and post-natal studies in rats. progeny of dams receiving oral (gavage) dose levels of 50 mg/kg (300 mg/m 2 or 1.6 times the maximum daily human tramadol dosage) or greater had decreased weights, and pup survival was decreased early in lactation at 80 mg/kg (480 mg/m m or 2.6 times the maximum daily human tramadol dosage). studies in pregnant rats that received oral acetaminophen during organogenesis at doses up to 1.3 times the maximum human daily dose (mhdd = 2.6 grams/day, based on a body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose- related increase in bone variations (reduced ossification and rudimentary rib changes). offspring had no evidence of external, visceral, or skeletal malformations. when pregnant rats received oral acetaminophen throughout gestation at doses of 1.9-times the mhdd (based on a body surface area comparison), areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses. these effects did not occur in animals that received oral acetaminophen at doses 0.5-times the mhdd, based on a body surface area comparison. in a continuous breeding study, pregnant mice received 0.25, 0.5, or 1.0% acetaminophen via the diet (357, 715, or 1430 mg/kg/day). these doses are approximately 0.7, 1.3, and 2.7 times the mhdd, respectively, based on a body surface area comparison. a dose-related reduction in body weights of fourth and fifth litter offspring of the treated mating pair occurred during lactation and post-weaning at all doses. animals in the high dose group had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next generation pups. tramadol hydrochloride and acetaminophen tablets are not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. tramadol and its metabolite, o-desmethyltramadol (m1), are present in human milk. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. the m1 metabolite is more potent than tramadol in mu opioid receptor binding [see clinical pharmacology ( 12.1)] . published studies have reported tramadol and m1 in colostrum with administration of tramadol to nursing mothers in the early post-partum period. women who are ultra-rapid metabolizers of tramadol may have higher than expected serum levels of m1, potentially leading to higher levels of m1 in breast milk that can be dangerous in their breastfed infants. in women with normal tramadol metabolism, the amount of tramadol secreted into human milk is low and dose-dependent. because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with tramadol hydrochloride and acetaminophen tablets. if infants are exposed to tramadol hydrochloride and acetaminophen tablets through breast milk, they should be monitored for excess sedation and respiratory depression. withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. following a single iv 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours post dose was 100 mcg of tramadol (0.1% of the maternal dose) and 27 mcg of m1. infertility use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. it is not known whether these effects on fertility are reversible [see adverse reactions ( 6.2), clinical pharmacology ( 12.2), nonclinical toxicology ( 13.1)] . the safety and effectiveness of tramadol hydrochloride and acetaminophen tablets in pediatric patients have not been established. life-threatening respiratory depression and death have occurred in children who received tramadol [see warnings and precautions ( 5.6)] . in some of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and one of the children had evidence of being an ultra-rapid metabolizer of tramadol (i.e., multiple copies of the gene for cytochrome p450 isoenzyme 2d6). children with sleep apnea may be particularly sensitive to the respiratory depressant effects of tramadol. because of the risk of life-threatening respiratory depression and death: - tramadol hydrochloride and acetaminophen tablets are contraindicated for all children younger than age 12 years of age [see contraindications ( 4)] . - tramadol hydrochloride and acetaminophen tablets are contraindicated for postoperative management in pediatric patient younger than 18 years of age following tonsillectomy and/or adenoidectomy [see contraindications ( 4)] . - avoid the use of tramadol hydrochloride and acetaminophen tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol unless the benefits outweigh the risks. risk factors include conditions associated with hypoventilation such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression. elderly patients (65 years of age or older) may have increased sensitivity to tramadol. in general, use caution when selecting a dosage for an elderly patient, 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. respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. titrate the dosage of tramadol hydrochloride and acetaminophen tablets slowly in geriatric patients and frequently reevaluate for signs of central nervous system and respiratory depression [see warnings and precautions ( 5.13)]. tramadol and acetaminophen are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. the pharmacokinetics and tolerability of tramadol hydrochloride and acetaminophen tablets in patients with impaired hepatic function have not been studied. based on information using tramadol immediate-release tablets in subjects with advanced cirrhosis of the liver, tramadol exposure was higher and half-lives of tramadol and active metabolite m1 were longer than in subjects with normal hepatic function [see clinical pharmacology ( 12.3)]. as tramadol and acetaminophen are both extensively metabolized by the liver, the use of tramadol hydrochloride and acetaminophen tablets in patients with hepatic impairment is not recommended [see warnings and precautions ( 5.9)] . the pharmacokinetics and tolerability of tramadol hydrochloride and acetaminophen tablets in patients with renal impairment has not been studied. based on studies using tramadol extended-release tablets, the excretion of tramadol and metabolite m1 is reduced in patients with creatinine clearance of less than 30 ml/min. in patients with creatinine clearances of less than 30 ml/min, it is recommended that the dosage of tramadol hydrochloride and acetaminophen tablets not exceed 2 tablets every 12 hours. [see dosage and administration (2.3)] . the total amount of tramadol and m1 removed during a 4 hour dialysis period is less than 7% of the administered dose based on studies using tramadol alone. monitor closely for signs of respiratory depression, sedation, and hypotension. tramadol clearance was 20% higher in female subjects compared to males in four phase 1 studies of tramadol hydrochloride and acetaminophen tablets in 50 male and 34 female healthy subjects. the clinical significance of this difference is unknown. tramadol hydrochloride and acetaminophen tablets contain tramadol, a schedule iv controlled substance. tramadol hydrochloride and acetaminophen tablets contain tramadol, a substance with potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [ see warnings and precautions ( 5.1) ]. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. misuse and abuse of tramadol hydrochloride and acetaminophen tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. the risk is increased with concurrent abuse of tramadol hydrochloride and acetaminophen tablets with alcohol and other cns depressants. abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. in addition, abuse of opioids can occur in the absence of addiction. all patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. patients at high risk of tramadol hydrochloride and acetaminophen tablets abuse include those with a history of prolonged use of any opioid, including products containing tramadol, those with a history of drug or alcohol abuse, or those who use tramadol hydrochloride and acetaminophen tablets in combination with other abused drugs. “drug-seeking” behavior is very common in persons with substance use disorders. 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 healthcare provider(s). “doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. tramadol hydrochloride and acetaminophen tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. risks specific to abuse of tramadol hydrochloride and acetaminophen tablets abuse of tramadol hydrochloride and acetaminophen tablets poses a risk of overdose and death. the risk is increased with concurrent use of tramadol hydrochloride and acetaminophen tablets with alcohol and/or other cns depressants. tramadol hydrochloride and acetaminophen tablets are approved for oral use only. parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and hiv. both tolerance and physical dependence can develop during use of opioid therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. do not abruptly discontinue tramadol hydrochloride and acetaminophen tablets in a patient physically dependent on opioids. rapid tapering of tramadol hydrochloride and acetaminophen tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. when discontinuing tramadol hydrochloride and acetaminophen tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of tramadol hydrochloride and acetaminophen tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. to improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. in patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [ see dosage and administration ( 2.5), and warnings and precautions ( 5.21) ]. infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [ see use in specific populations ( 8.1)].

United States - English - NLM (National Library of Medicine)

endo pharmaceuticals inc. - testosterone (unii: 3xmk78s47o) (testosterone - unii:3xmk78s47o) - testosterone 10 mg in 0.5 g - fortesta is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: - primary hypogonadism (congenital or acquired) – testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol, heavy metals. these men usually have low serum testosterone concentrations and gonadotropins (follicle stimulating hormone [fsh] and luteinizing hormone [lh]) above the normal range. - hypogonadotropic hypogonadism (congenital or acquired) – gonadotropin or luteinizing hormone-releasing hormone (lhrh) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. these men have low serum testosterone concentrations but have gonadotropins in the normal or low range. limitations of use - safety and efficacy of fortesta in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. - safety and efficacy of fortesta in males <18 years old have not been established [see use in specific populations (8.4)] . - fortesta is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate [see warnings and precautions (5.1) and adverse reactions (6.1)] . - fortesta is contraindicated in women who are pregnant. testosterone can cause virilization of the female fetus when administered to a pregnant woman [see use in specific populations (8.1, 8.2)] . risk summary fortesta is contraindicated in pregnant women. testosterone is teratogenic and may cause fetal harm based on data from animal studies and its mechanism of action [see contraindications (4) and clinical pharmacology (12.1)] . exposure of a female fetus to androgens may result in varying degrees of virilization. in animal developmental studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. these studies did not meet current standards for nonclinical development toxicity studies. data animal data in developmental studies conducted in rats, rabbits, pigs, sheep, and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. structural impairments observed in females included increased anogenital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. increased pituitary weight was seen in both sexes. testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy. risk summary fortesta is not indicated for use in females. infertility during treatment with large doses of exogenous androgens, including fortesta, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see warnings and precautions (5.8)] , possibly leading to adverse effects on semen parameters including sperm count. reduced fertility is observed in some men taking testosterone replacement therapy. testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see drug abuse and dependence (9.2)] . with either type of use, the impact on fertility may be irreversible. the safety and efficacy of fortesta in pediatric patients <18 years old has not been established. improper use may result in acceleration of bone age and premature closure of epiphyses. there have not been sufficient numbers of geriatric patients involved in controlled clinical studies utilizing fortesta to determine whether efficacy in those over 65 years of age differs from younger subjects. of the 149 patients enrolled in the pivotal clinical study utilizing fortesta, 20 were over 65 years of age. additionally, there are insufficient long-term safety data in geriatric patients to assess the potential risks of cardiovascular disease and prostate cancer. geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of bph. no studies were conducted in patients with renal impairment. no studies were conducted in patients with hepatic impairment. fortesta contains testosterone, a schedule iii controlled substance in the controlled substances act. drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. abuse and misuse of testosterone are seen in male and female adults and adolescents. testosterone, often in combination with other anabolic androgenic steroids (aas), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. there have been reports of misuse of men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. abuse-related adverse reactions serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility, and aggression. the following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. the following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. the following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. behaviors associated with addiction continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: - taking greater dosages than prescribed - continued drug use despite medical and social problems due to drug use - spending significant time to obtain the drug when supplies of the drug are interrupted - giving a higher priority to drug use than other obligations - having difficulty in discontinuing the drug despite desires and attempts to do so - experiencing withdrawal symptoms upon abrupt discontinuation of use physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. drug dependence in individuals using approved doses of testosterone for approved indications has not been documented. instructions for use fortesta® (for-tes-ta) ciii (testosterone) gel for topical use read this instructions for use for fortesta before you start using it and each time you get a refill. there may be new information. this leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment. applying fortesta: - apply fortesta only to areas that will be covered by shorts or pants. - fortesta should be applied to the front and inner part of your thighs only. do not apply fortesta to the area of the thigh closest to the scrotum. do not apply fortesta to any other parts of your body such as your stomach area (abdomen), penis, scrotum, shoulders or upper arms. - apply fortesta in the morning. if you shower or bathe, fortesta should be applied afterwards. - avoid swimming, showering, or bathing for at least 2 hours after you apply fortesta. - fortesta is flammable until dry. let fortesta dry before smoking or going near an open flame. - wash your hands with soap and water right after you apply fortesta. - before using a new canister of fortesta for the first time, you will need to prime the pump. to prime the fortesta pump, gently push down on the pump 8 times. do not use any fortesta that comes out while priming. wash it down the sink or throw it in the trash to avoid accidental exposure to others. your fortesta pump is now ready to use. - use fortesta exactly as your healthcare provider tells you to use it. your healthcare provider will tell you the dose of fortesta that is right for you. - press down on the pump to apply the medicine directly on clean, dry, skin that is not broken on the front and inner part of your thighs. use 1 finger to gently rub fortesta evenly onto the front and inner part of each thigh. - let the application site dry completely before putting on shorts or pants. - wash your hands right away with soap and water. how should i store fortesta? - store fortesta at room temperature between 68ºf to 77ºf (20ºc to 25ºc). - when it is time to throw away the canister, safely throw away used fortesta in the household trash. be careful to prevent accidental exposure of children or pets. - keep fortesta away from fire. - do not freeze fortesta. keep fortesta and all medicines out of the reach of children. this instructions for use has been approved by the u.s. food and drug administration. revised: 05/2019