Talwin Injection

Pregnancy

Risk Summary

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with TALWIN in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

In animal reproduction studies, pentazocine administered subcutaneously to pregnant hamsters during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 4.4 times the maximum daily dose [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 2–4% and 15–20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Prolonged use of opioid analgesics 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 of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.3)].

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. TALWIN is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including TALWIN, 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. Patients receiving TALWIN during labor have experienced no adverse effects other than those that occur with commonly used analgesics.

Data

Animal Data

In a published report, a single dose of pentazocine administered to pregnant hamsters on Gestation Day 8 increased the incidence of neural tube defects (exencephaly and cranioschisis) at a dose of 196 mg/kg, SC (4.4-times the maximum daily dose (MDD) of 360 mg/day pentazocine on a body surface area basis). No evidence of neural tube defects were reported following a dose of 98 mg/kg (2.2 times the MDD).

Lactation

Risk Summary

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TALWIN and any potential adverse effects on the breastfed infant from TALWIN or from the underlying maternal condition.

Clinical Considerations

Infants exposed to TALWIN through breast milk 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.

Females and Males of Reproductive Potential

Infertility

Chronic use of opioids 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)].

Pediatric Use

The safety and efficacy of TALWIN as preoperative or preanesthetic medication have been established in pediatric patients 1 to 16 years of age. Use of TALWIN in these age groups is supported by evidence from adequate and controlled studies in adults with additional data from published controlled trials in pediatric patients. The safety and efficacy of TALWIN as a premedication for sedation have not been established in pediatric patients less than one year old. Information on the safety profile of TALWIN as a postoperative analgesic in children less than 16 years is limited.

Geriatric Use

Pentazocine is metabolized in the liver and excreted primarily in the urine. Patients with impaired renal or hepatic function may have slower elimination of the drug, and the risk of adverse reactions to this drug may be greater in these patients. Elderly patients (aged 65 years or older) may have increased sensitivity to pentazocine. 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 TALWIN slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.5)].Pentazocine 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.

Controlled Substance

TALWIN contains pentazocine, a Schedule IV controlled substance.

Abuse

TALWIN contains pentazocine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone and tapentadol. TALWIN can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.1)].

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.

Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

"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 health care provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers 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.

TALWIN, like other opioids, can be diverted for non-medical 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 re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Talwin Injection

Abuse of TALWIN poses a risk of overdose and death. The risk is increased with concurrent abuse of TALWIN with alcohol and other central nervous system depressants.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. 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). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (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 opioid usage.

TALWIN should not be abruptly discontinued in a physically-dependent patient [see Dosage and Administration (2.4)]. If TALWIN is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and 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.

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)].

Talwin Injection contains pentazocine lactate, a partial opioid agonist. Pentazocine is a member of the benzazocine series (also known as the benzomorphan series).

Chemically, pentazocine lactate is 1, 2, 3, 4, 5, 6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol lactate, a white, crystalline substance soluble in acidic aqueous solutions, and has the following structural formula:

C19H27NO∙HCl           Molecular Weight: 321.88

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term animal studies to evaluate the carcinogenic potential of pentazocine have not been conducted.

Mutagenesis

Studies to evaluate the mutagenic potential of pentazocine have not been conducted.

Impairment of Fertility

Animal studies to evaluate the impact of pentazocine on fertility have not been conducted.

TALWIN (pentazocine) 30 mg/mL for injection is supplied as:

The pH of TALWIN solutions is adjusted between 4 and 5 with lactic acid or sodium hydroxide. The air in the ampuls and vials has been displaced by nitrogen gas.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see Drug Interactions (7)].

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions (6), Clinical Pharmacology (12.2)].

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-0855-1.0

Consult your pharmacist.

How to use Talwin Vial

Consult your pharmacist.

Consult your pharmacist.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.