TARGINIQ ER (Page 5 of 11)

5.13 Risks of Driving and Operating Machinery

​ TARGINIQ ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of TARGINIQ ER and know how they will react to the medication [see Patient Counseling Information (17)].

5.14 Laboratory Monitoring

​ Not every urine drug test for “opioids” or “opiates” detects oxycodone reliably, especially those designed for in-office use. Further, many laboratories will report urine drug concentrations below a specified “cut-off” value as “negative”. Therefore, if urine testing for oxycodone is considered in the clinical management of an individual patient, ensure that the sensitivity and specificity of the assay is appropriate, and consider the limitations of the testing used when interpreting results.

6 ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling:

• Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)]
• Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)]
• Interactions with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions (5.4)]
• Adrenal Insufficiency [see Warnings and Precautions (5.7)]
• Severe Hypotension [see Warnings and Precautions (5.8)]
• Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.10)]
• Seizures [see Warnings and Precautions (5.11]
• Withdrawal [see Warnings and Precautions (5.12)]

6.1 Clinical Trial 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.

A total of 2,396 patients were treated in controlled and open-label clinical studies with TARGINIQ ER. Seven hundred and ninety-four of these patients (33%) were treated for approximately six months and 621 (26%) were treated for approximately one year.

TARGINIQ ER may increase the risk of serious adverse reactions such as those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, or shock [see Overdosage (10)].

Commonly Observed Treatment-Emergent Adverse Reactions in a Clinical Study with TARGINIQ ER in Opioid-Experienced Patients with Uncontrolled Moderate to Severe Chronic Low Back PainThe safety data described in Table 4 below are based on a 12-week, randomized, double-blind, placebo-controlled clinical trial in opioid-experienced patients with moderate to severe chronic low back pain. This trial included 1,095 TARGINIQ ER-treated patients in an open-label titration period, and 298 TARGINIQ ER-and 302 placebo-treated patients in a double-blind treatment period. The mean age was 52 years old; 55% were female, and 45% were male; 74% were Caucasian, 22% were Black, and 11% were Hispanic.

The most common treatment-emergent adverse reactions (reported by ≥ 5% of TARGINIQ ER subjects) during the open-label or double-blind periods were nausea and vomiting.

The most common reason for discontinuation during the open-label period due to treatment-emergent adverse reactions (reported by ≥ 1% of subjects) was nausea (2%).

The most common reason for discontinuation during the double-blind period due to treatment-emergent adverse reactions (reported by ≥ 1% of subjects with TARGINIQ ER or placebo) was drug withdrawal syndrome (<1% vs. 1%), respectively.

The incidence of treatment-emergent adverse reactions reported by ≥ 2% of subjects in a clinical trial comparing TARGINIQ ER with placebo is shown in Table 4 below:

Table 4. Incidence of Treatment-Emergent Adverse Reactions Reported in >2% of Subjects Taking TARGINIQ ER: Safety Population (Open-Label Titration Period) and Randomized Safety Population (Double-Blind Period)

*Percentages in the table are based on adverse reaction reports of Drug Withdrawal Syndrome in the key efficacy and safety study. In addition to the adverse reaction reports, an independent Adjudication Committee identified additional subjects with possible drug withdrawal syndrome, resulting in a total (adverse reactions plus adjudicated cases) of 2% of subjects in the Open-Label Period, and in the Double-Blind Period 4% of subjects treated with TARGINIQ ER and 2% treated with placebo.
		Open-Label Period		Double-Blind Period
		TARGINIQ ER (N=1095) (%)		Placebo (N=302) (%)	TARGINIQ ER (N=298) (%)
MedDRA System Organ Class
	Preferred Term
	Nausea	7		5	8
	Headache	4		3	3
	Constipation	3		1	3
	Abdominal pain	3		2	3
	Vomiting	2		2	5
	Pruritus	2		1	2
	Anxiety	1		0	3
	*Drug withdrawal syndrome	1		2	3
	Insomnia	1		1	2
	Back pain	0		1	3

In a clinical trial, the following adverse reactions were reported in patients treated with TARGINIQ ER with an incidence between ≥ 1% and <2%:

Eye disorders: lacrimation increased
General disorders and administration site conditions: fatigue
Infections and infestations: influenza
Injury, poisoning, and procedural complications: fall
Musculoskeletal and connective tissue disorders: arthralgia
Nervous system disorders: dizziness, sinus headache, somnolence
Psychiatric disorders: drug abuse
Skin and subcutaneous tissue disorders: pruritus, rash, cold sweatVascular disorders: hot flush, hypertension