Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

TEKTURNA HCT (NDA-022107)

(ALISKIREN HEMIFUMARATE; HYDROCHLOROTHIAZIDE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

Download Data

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09/28/2020 (SUPPL-34)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Post-Marketing Experience

(Newly added information)

Non-melanoma Skin Cancer: Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer. In a study conducted in the Sentinel System, increased risk was predominantly for squamous cell carcinoma (SCC) and in white patients taking large cumulative doses. The increased risk for SCC in the overall population was approximately 1 additional case per 16,000 patients per year, and for white patients taking a cumulative dose of ?50,000mg the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(Newly added information)

Non-melanoma Skin Cancer: Instruct patients taking hydrochlorothiazide to protect skin from the sun and undergo regular skin cancer screening.

Patient Information

(Newly added information)

Protect your skin from the sun and undergo regular skin cancer screening, as one of the medicines in Tekturna HCT may cause non-melanoma skin cancer.

11/04/2016 (SUPPL-29)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Fetal Toxicity

Aliskiren (addition of subheading)

Use of drugs that act …

Hydrochlorothiazide (addition of subheading)

Thiazides cross the placenta …

6 Adverse Reactions

6.2 Post-Marketing Experience

Aliskiren

Hypersensitivity: addition of hyponatremia

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

Tekturna HCT can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the reninangiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Tekturna HCT as soon as possible.

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 malformations and miscarriage in clinically recognized pregnancies is 2-4%, and 15-20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal adverse reactions

Aliskiren

Use of drugs that act on the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy …

In patients taking Tekturna HCT during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Tekturna HCT for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur in neonates with a history of in utero exposure to Tekturna HCT, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function.

Hydrochlorothiazide

Thiazides cross the placenta …

Data

Animal Data

No reproductive toxicity studies have been conducted with the combination of aliskiren and HCTZ. However, these studies have been conducted for aliskiren and HCTZ alone.

Aliskiren

In developmental toxicity studies, pregnant rats and rabbits received oral aliskiren hemifumarate during organogenesis at doses up to 20 and 7 times the maximum recommended human dose (MRHD) based on body surface area (mg/m2), respectively, in rats and rabbits. (Actual animal doses were up to 600 mg/kg/day in rats and up to 100 mg/kg/day in rabbits.) No teratogenicity was observed; however, fetal birth weight was decreased in rabbits at doses 3.2 times the MRHD based on body surface area (mg/m2). Aliskiren was present in placentas, amniotic fluid and fetuses of pregnant rabbits.

HCTZ

When pregnant mice and rats were given HCTZ …

These animal studies were conducted according to the standards of the time.

8.2 Lactation

(PLLR conversion)

Risk Summary

There is no information regarding the presence of Tekturna HCT or aliskiren in human milk, the effects on the breastfed infant, or the effects on milk production. Limited published studies report that hydrochlorothiazide is present in human milk. However, there is insufficient information to determine the effects hydrochlorothiazide on the breastfed infant or the effects of hydrochlorothiazide on milk production. Because of the potential for serious adverse reactions, including hypotension, electrolyte imbalances and renal impairment in nursing infants, advise a nursing woman that breastfeeding is not recommended during treatment with Tekturna HCT.

8.4 Pediatric Use

Safety and effectiveness of Tekturna HCT in pediatric patients have not been established.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

Patient Counseling Information

Lactation (Addition)

Advise nursing women that breastfeeding is not recommended during treatment with Tekturna HCT.

Patient Information

Tekturna® HCT (tek-turn-a HCT) (aliskiren and hydrochlorothiazide) Tablets

What are the possible side effects of Tekturna HCT?

Less common side effects include skin rash, severe skin reactions (signs may include severe blistering of the lips, eyes or mouth, rash with fever and skin peeling), liver disorder (signs may include nausea, loss of appetite, dark colored urine or yellowing of skin and eyes) and low level of sodium in blood. (addition underlined)